The document discusses the implementation of a POMS MES system at Almirall, a pharmaceutical company. It describes how the MES system improved quality and production operations through integrated management of processes like purchasing, manufacturing, quality control and logistics. Key benefits included improved traceability, compliance and flexibility to remain competitive through continuous optimization of manufacturing execution.

1. David Badia, ASESA , & Xavier Raso, ALMIRALL POMS MES helps improve results in daily manufacturing operations of Pharmaceutical Industry

2. Agenda Vision and Experience of MES Mr. Xavier Raso IS Business Process Manager ALMIRALL Pharmaceutical Company POMS MES implementation succeed Mr. David Badia Industrial Engineer & Consultant ASESA Sistemas

3. Agenda Vision and Experience of MES Mr. Xavier Raso IS Business Process Manager ALMIRALL Pharmaceutical Company POMS MES implementation succeed Mr. David Badia Industrial Engineer & Consultant ASESA Sistemas

4. Our mission To provide society with innovative medicines that help to improve people’s health and quality of life.

5. Our corporate values Professionalism Innovation and creativity Effectiveness and agility Teamwork Leadership Customer focus Transparency

6. Our goals Forward looking, future focused Potentiate our R&D Expand our international presence Maintain our position as leaders in Spain

7. Our centres Headquarters: R&D Centers: Chemical plants: Pharmaceutical plants: Affiliates: Barcelona Sant Feliu de Llobregat Bad Homburg (Germany) Reinbek (Germany) Chemical Synthesis Unit in Sant Just Desvern Active Ingredient Scaling-up Unit in Sant Andreu de la Barca Sant Andreu de la Barca Sant Celoni Sant Andreu de la Barca Sant Just Desvern Reinbek (Germany) Austria, Belgium, France, Germany, Italy, Mexico, Poland, Portugal, Spain, Switzerland and the United Kingdom-Ireland.

8. Major milestones Creation of the affiliate in Italy 2002 Creation of the affiliate in Mexico and acquisition of the affiliate in France 2001 Launch of almotriptan 2000 Merger between Almirall and Prodesfarma 1997 Creation of the affiliate in Portugal 1993 Launch of aceclofenac 1992 Launch of ebastine Acquisition of the affiliate in Belgium 1990 Laboratorios Almirall starts activity 1944 Opening of affiliates in Austria, Poland, Switzerland and the United Kingdom-Ireland 2008 Onto the Stock market and listed on the Spanish Continuous market Acquisition of Hermal, the European prescription dermatology business of Reckitt Benckiser Acquisition of a portfolio of 8 products from Shire plc 2007 Official opening of the new R&D Centre in Sant Feliu de Llobregat Acquisition of the Inhaler Development Unit in Bad Homburg (Germany) 2006 Creation of the affiliate in Germany 2003

9. Human resources 3.300 employees 15% of the workforce is in R&D Over 40% of the workforce is outside Spain

10. Our research therapeutic focus Current research programmes are focused on the discovery of novel drugs that will treat illnesses like: Asthma Chronic obstructive pulmonary disease (COPD) Rheumatoid arthritis Multiple sclerosis Psoriasis and other dermatology indications

11. Health & Environment Prevention of risks at work Strategic and priority factor. TÜVRheinland certificate which attests the conformity of its Occupational Risk Prevention Management System to the international standard OHSAS 18001. Environment Protection and respect of the environment is one of our main commitments. ISO 14001:2004 certification for environmental management of activities.

12. Manufacturing Area of ALMIRALL “ Imagination is more important than knowledge” (Albert Einstein)

13. Pharmaceutical products 239 pharmaceutical specialties (*) 543 presentations (*) 57 countries 89.3 million units of finished product 3.5 million units in bulk (**) Third parties included

14. Pharmaceutical Plant Sant Andreu de la Barca (Barcelona) Renovation / Enlargement in 1994 Highly automated Number of units (million units): 50

15. Business Processes: Purchase to reception Purchase orders and delivery manag.. Goods reception (physical) Quality control Invoice acceptance Purchasing SAP R/3 ERP LIMS Laboratory POMS MES Modules QA team SLM Logistics Master Data maintenance (products, warehouses, etc) Purchasing planning (for production needs) Purchase order process Material reception Stocks management Invoice acceptance Pallets configuration Bulk identification Warehousing conditions Pallet availability Stocks management QA batch creation Automatic warehousing (link with silo) Analysis specifications Analytical profile per supplier Lab task assignment Register analytical results Register batch acceptance Operations for samples Supply chain Labx Instrumental Instrumental management

16. Business Processes: Manufacturing Production Orders management Dispending raw material (physical) Production process Quality control Modules SAP R/3 POMS MES LIMS QA team SLM Batch warehouse selection Automatic movements of goods from warehouse to production line Pallets management for finish product Boxes management Automatic movements of finish product from production line to warehouse (including AMD system) Weight production guides Formulation and doses production guide Supply chain Production orders fulfillment FW Master Data maintenance (products, warehouses,etc Production order processes Stocks management Production cost managemant Detailed transaction Production process control in Production line Finish + intermediate product Analysis Acceptance batch

17. Objectives of the POMS MES System Improve Quality Guiding the operator Traceable processes Safer process Single view of reality Highly flexible planning. Compliance with a regulatory environment increasingly demanding (GAMP, FDA) Integration with all manufacturing systems

18. Integration levels in manufacturing process POMS Production guide and Process management SLM Materials and components procurement SCADA Syrups formulation SCADA Sachets formulation SCADA Cream formulation PLC Syrups Formulation control PLC Sachets Formulation control PLC Cream Formulation control PLC BIN unload active stations control Syrups manufacturing reactors Sachets manufacturing reactors Cream manufacturing reactors BIN unload station BIN unload station Operator PLC Materials Transport control AMD Automatic guided vehicles Materials Transport

19. Scope of implementation of POMS MES QC Sampling: 3 cabins Weigh&dispense: 4 Cabins Liquid formulation: 3 Modules Solid formulation: 1 Module Doses production: 6 Modules

20. Milestones of POMS MES in ALMIRALL 1994: First Implementation of POMS MES in Sampling and Weigh. Intel 80386/486, Windows 3.1, OS/2 2.1, POMS MES 2.1 1998: Scope increased of MES system to Formulation and Dosing. 1999: Server exchange. Performance and capacity. 2001: Server exchange. Upgrade of all management systems of plant. 2003: QC Sampling process to new platform of POMS MES 5 Windows Xp SP2, OPC server, Windows 2003 server, POMS MES 5.1 2004 – 2006: Weigh, Formulation and Dispensing to POMS MES 5 2007 – 2008: Improvements and upgrade to current POMS MES 5.2 Windows Xp SP2, OPC server, Windows 2003 server, POMS MES 5.2 2009 – future: continuous improvement, new areas, new sites, …

21. Agenda Vision and Experience of MES Mr. Xavier Raso IS Business Process Manager ALMIRALL Pharmaceutical Company POMS MES implementation succeed Mr. David Badia Industrial Engineer & Consultant ASESA Sistemas

22. Key MES focus It’s all about performance in daily Manufacturing operations. Because only through improved Execution you can remain competitive and vital. Matching Systems and knowledge ensuring production in the right way, at the right time, every time. WHAT WHY HOW

23. Why Honeywell POMS MES ? Leading MES Solution for Life Sciences. Modular and scalable solution to drive plant’s continuous improvement process. High added value ready to use: Production recipes and manufacturing guides based on SOP with more than 50 standard actions and Best Practice Objects (BPO). Multiple weigh methods, batch or campaign, scaling, compensating, clean. eBatch record (EBR), exception mgt., lot traceability, genealogy. Web-based information reporting for paperless plant operation. In-Process Control (IPC) and Statistical Process Control (SQC) Based on a development platform that enables very flexible integration with customer new and legacy operations: Up from corporate ERP, LIMS, WMS, Scheduler, SCM, … Down to plant assets, scales, barcode, label printers, Scada & PLC / OPC. Certified product for easier system’s validation. Audit Trail, Domain Security, 21CFR11 compliance, eSignature.

24. SOLID FORMS FORMULATION OPERATION Information flows across plant resources MFTG. ORDER SCHEDULING RECIPE MANAGING QC SAMPLING OPERATION WEIGH & DISPENSE OPERATION SOLID DOSING OPERATION LIQUID FORMS FORMULATION OPERATION QUALITY CONTROL PRODUCTION SUPERVISION

25. QC Sampling Operation 3 cabins with climate control. Automatic reception and evacuation of raw material, tool kit and trash containers. Material safety handling and PPE. Cabin climate conditions monitor. Cabin and asset cleaning control. Lot and NIR identification. Visual properties qualification. Raw material sampling execution. Carrier and bags barcode labelling. QC Sampling report. LIMS and SAP interface.

26. Recipe Edition and Management Weigh, formulation and dispensing recipe edition. Paperless manufacturing guide implementation. General Unit Procedure. Bill of Equipment (BOE). Use of action list with steps Instructions with check-in lists. Signatures (initial, single, double) eDocuments: Standard operation procedures (SOP), material safety data sheets (MSDS), process synoptic graphs and other specs. Recipe review and approval cycle.

27. Manufacturing Orders Scheduling Orders are released from the ERP based on plant capacity. Automatic generation of mfgt. orders in the POMS MES system. Batch generation for weight, liquid formulation, solid formulation and solid dosing operations. Assignment of related process unit. Exception monitoring. Procedure traceability.

28. Weigh & Dispense Operation 4 weigh cabins: 1 for Ex materials and 1 for big-bags. Weighs to order or to ticket. Weighs in bags and recipients. Direct weighs in BIN container. Registration of raw material and box carriers. Material safety handling and PPE. Cleaning control of cabin & assets. Automated BIN movement control. Scale connection, calibration and standardization. WIP Container barcode labelling. Certified weigh order report.

29. Liquids Formulation Operation 3 formulation areas: syrups, sachets and creams. Manufacturing eGuide by actions Check-in process unit and assets. Registration of raw material and WIP containers. Cleaning control of cabin & assets. Automated BIN movement control. Control of formulation batch phases through process SCADA. Sampling collection for QC analysis during process execution. Formulation batch report.

30. Solids Formulation Operation 2 formulation lines: dryer line and mixer line. Combined or separated operation. Manufacturing eGuide by actions Check-in process unit and assets. Registration of raw material and WIP containers. Minor raw materials preparation in auxiliary tank. Cleaning control of cabin & assets. Automated BIN movement control. Formulation batch report.

31. Solids Dosing Operation 6 dosing lines: tablets, capsules and sachets. Manufacturing eGuide with process synoptic and product specs. Check-in process unit and assets. Registration of conditioning material and empty drum carriers. Units registration of bags and drums with barcode labels. Control of dose weigh. Waste reporting and mass yield calculation of batch. Dosing batch report.

32. Production supervision Support during execution of manufacturing orders. Exception management. Review of Production reports. Verification and acceptance of incidences. Production report approval. Order / Batch release to next step.

33. MES to Plant equipment interfaces MES QC Sampling Formulation and Dosing PLANT CONTROL SYSTEMS Sample Collection Production Process Control: SCADA system of Liquids Formulation SAS control of carriers of raw materials, containers and tools Weigh and Dispense Weigh and dispense Climate Control / Environment parameters monitoring Supervision and/or control of Loading / Unloading stations of BIN carriers Connection to scales and balances POMS MES System

34. Automated BIN control interface Plant equipment interfaces Scale control interface Liquid Formulation Batch process control interface

35. Communication through database. More than 300 functions stored. Data exchange of manufact. orders including Bill of Materials (BOM) Request of material movement to warehouse and local logistics. Raw material carrier and pallet exchange through SAS cabin doors. BIN carrier movements by Automated Guided Vehicles (AGV). Barcode identification of containers and BIN carriers. Check of Quality Control in Full Released Status. Assignment of materials in bags and containers. Raw material and WIP container consumption. MES to SAP and logistics interface

36. Preparation and Planning Quality Plan Planning Specification Functional Specification: Functions, Data and Interfaces. Basic Design Specifications of Hardware Traceability Matrix: Requirements vs. Functions Design, Implementation, Construction and Test Design Specifications of Software Design Specifications of Hardware Equipment Construction and Installation manuals Configuration and programming Risk analysis 21 CFR 11 Protocol Design: UT, FAT, SAT, DQ , IQ , OQ , SIT, PQ Execution DQ, UT, FAT Installation and Final Acceptance Installation of system in production Execution SAT, IQ, OQ, SIT, PQ Adjustments MES System lifecycle and documentation System’s Qualification for regulatory compliance

37. Technological infrastructure update (equipment, hardware & software) Standard POMS MES package customizations required. Logistics System integration. Minimal interferences with plant production planning. System Qualification and Validation for regulatory compliance. Need to have a of plant personnel. Communication with legacy equipments, systems and installations. International supplier with a recently new local integrator of POMS. Standardization and homogenization of the system among the processes. Project scope spitted in 3 phases for shorter milestones, visible results: (1º) QC / Sampling, (2º) Weigh & Dispense, (3º) Formulation and Dosing. Specialized consultancy: intensive work vs constant work, consultancy costs vs training costs. Evaluation of the real effort with an assumable planning for everybody. Creation of a multidisciplinary human team for the project. Certified technical training and practical learning by doing. Analysis of requirements in depth. Realignment with the standard MES product functionality to reduce customizations. Challenges and solutions

38. ++++++ Together forward in the way of manufacturing excellence Results and benefits Guided “lean” manufacturing + agility Operation’s execution with quality and safety + efficacy Notification, diagnosis, solution of incidences + efficiency Visibility of assets and work in process + transparency Impulse the continuous improvement + creativity Support service and direct help to users + customer focus

39. Imagination is what makes all things possible! Thank You, for more information please contact us Xavier Raso [email_address] David Badia [email_address] www.almirall.com www.asesa.net