System Impact Assessment Revision Index and Change Record Revision Date Reason for revision 00 New Document Distribution List Name Position / Company ‘Copy 1 2 OriginalTable of Contents Nooauna 10 Revision Index and Change Record. Distribution List .. Approval Signature Introduction. Scope Responsibility. Definitions and abbreviations 7.1 Definitions .. 7.2 Abbreviations... References System Impact Assessment Methodolog) 9.1 Introduction... 9.2 System identification. 9.3. System rating... 9.4 Impact assessment rating for process and building systems. System Impact Assessment. renriS)- Approve this document. Definitions and abbreviations System Boundary Barrier Impact Assessment Indirect Impact No Impact Option A group of individual items of equipment or processes (sub- systems) united by some interaction or interdependence, performing many actions but that function as a single unit. Also applies to a disciplined and pre planned approach to undertake any task. A limit drawn around a system to logically define what is, and is not, included in the system. A barrier controls the impact from a linked system onto a Direct Impact System by measures or features preventing an impact on the quality of product, process results, and data of medicinal agency concern and on compliance (e.g. an alarm and a corrective action). Barriers are considered critical aspects. The process of evaluating the impact of the operating, controlling, alarm, and failure conditions of a system, on the quality of the product. By product is meant a pharmaceutical product or components included in the pharmaceutical product (e.g., purified water). Equipment and system assessed to have at least one critical feature (e.g. systems with product contact, systems involved with product processing, supplies with product contact, fermentation, product purification, water for injection, formulation, HPLCs). Equipment and systems isolated from direct impact systems by an upstream barrier (e.g. cooling water, instrument air for equipment operation). Systems where barrier is obvious, and needs no further consideration (e.g. offices, elevators, canteens), Functions or systems where the final decision about integration in the scope isn’t made. 7.2 Abbreviations AHU enc NC Air Handling Unit Controlled Not Classified Not ClassifiedBMS Building Management System FF Fire Fighting FMS. Facility Monitoring System HVAC Heating, ventilation and Air Conditioning ISPE International Society for Pharmaceutical Engineering ups. Uninterrupted Power System References [1] _ ISPE Baseline Guide, volume 5, “Commissioning and qualification”. [2] Validation Project Pian, UIP solid and liquid oral dose plant- D105-AS-VPP- oot [3] VSIP II Project General Technical User Requirements. Document received by TVC 19 Oct 2009 System Impact Assessment Methodology 9.1 Introduction This section describes the requirements from the ISPE guideline “Commissioning and Qualification, volume 5”, ref. [ 1]. Equipment and systems shall be rated according to the definition in sections 7: : Direct Impact - Indirect Impact - No Impact The system is rated direct impact The system and barriers must be qualified, The system is rated indirect impact The system must undergo commissioning and the barrier must be qualified. The system is rated no impact The system and barriers must undergo commissioning. If an entire module/system, a part hereof or a component is assessed as Indirect Impact, the barrier between Direct and Indirect Impact must be identified and documented. If the barrier itself is not a part of the direct Impact system, the Indirect Impact system must be upgraded to Direct Impact.9.2 System identification System identification shall be done according to General Technical User Requirements, ref.[ 3 ]. The General Technical User Requirements is a breakdown of the physical plant into function-related objects - equivalent to the systems defined in this document. 9.3 System Rating In ISPE's guideline the following questions listed in table can be asked for a system to rate the impact on the product quality (impact assessment) for each system. The system has direct contact with the product. ‘The system provides an excipient or produces an ingredient or solvent The system is used in cleaning or sterilizing. . The system preserves product status. The system produces data which is used to accept or reject product. The system is a process control system that may affect product quality and there is no system for independent verification of control system performance in place. 1. 2 3. 4, 5. 6. If the answer is YES to any of these questions then the system has direct impact on product quality. If the answer is No to all of these questions then the system could be either indirect impact or no impact. A rationale for either indirect impact or no impact these must be described. At systems with indirect impact this additional rationale must include a description of the barrier. 9.4 Impact assessment rating for process and building systems The questions described in section 9.1 will be answered for each system. The flow diagram for answers to the questions in section 9.1 and what the impact assessment will be according to the answers of the questions is listec as bellow.The questions must be answered until the first coming answer is YES. In addition to the answer there must be a rationale for the answer. A Yes in the last question asked for this system will demand that the system must be rated as a system with direct impact. If all 6 questions can be answers with a No, a rationale rating the system either indirect or no impact must be described to answer if the system has indirect or no rationale must ‘The system has direct contact with the product_ | —¥€8——» Direct tmpact No ——___» The system provides an Excipient or Yes i procedures an Inaredient or solvent Direct tmpact [no The system is used in cleaning orstertizing. | —¥®8 > rect impact No +. Yes “The system preserves product status. Direct Impact Tne “The system produces data which isusedto |_Yes 5 pipe acceot or relect product. ea J No The system is @ process control systern that ve may affect product qualty and there i no = system for Independent verfeation of control | ———>_irect Impact system performance in place No LM __y indirect Direct Impact / no impact impact on product quality. For systems with indirect impact tl include a description of the barriers.10 System Impact Assessment “Generate purified water for process and cleaning Provide sof water for Purified water generation ‘Provide puriied water for ‘process and cleaning storage and distribution system Compress | Process air_[¥ Y Ww Y W w Dred ‘Sterile filter wil | For transfer of coating alr distribution Impact be located at | solution to tablets, spray system the Interface | binder into HMG, to blow between bottles, to blow a mould on qualification | the Blister. and ‘commissioning.itself will never be in product contact, but regulates critical temperatures. Barner is ‘temperature ‘control on. critical ‘equipment. Utlized for temperature regulation of utlity systems ‘Black steam system Black seam distribution system Tadreck impact Black Steam IRself will never be in product ‘contact, but regulates ertical temperatures. Barter is ‘temperature control on certical Keep temperature for process, etc. equipment.valve is the process and instrument barrier. Tir contror For instrament valve is the barter, WA Wo Impact te product quality Dust Waste Potential | Confirm Potential impact to product Collector | Powder Impact ‘Acceptability | quality only confirmed during Collection, during PQ” | operation BMS BMS Trdirect [N/A Engineering monitoring of impact HVAC or utilities, access Control, some procedures wil be manual. Building | Production | Production Direct Wa “The building Includes the Building | Building impact class D room. The walls, floors and ceiling will be prepared to support this Foom class. Installation {Qualifcation of the rooms will ‘be performed to confirm the‘area requirements, Direct WA Environment within the Building | Material impact sampling booth to be Sampling qualified, Raw Tndirect | The ‘A thermal mapping 1s Materials Impact temperature in_| expected to be performed in Warehouse the cool whole of warehouse area. storage rooms/ ‘area must be monitored and validated. Packaging Tndirect | The "Temperature can impact Materials impact temperature in| stability of packaging Warehouse the cool materials. “A thermal storege rooms/ | mapping is expected to be ‘area must be | performed in whole of, ‘monitored and | warehouse area, validated. Finish Good Indirect [The ‘Athermal mapping © Warehouse impact temperature in| expected to be performed in the area must | whole of warehouse area, be monitored and validated. Qc Lab No impact [N/A Tio impact to product quality“Administrats Tnclude administration office, canteen, etc, ‘No impact to product quality Building | Electrical | Electrical No impact | NVA Wo impack t product quality ‘Support ‘Security | Caw No impact | N/A Wo impact to product quality ‘Surveillance 5 e fivac Ventilation Direct Barrier willbe | Taclude Classified room to and impact qualified HEPA, | preserve the room status, Conditionin Airflow, ‘Open product handling (*] 9 Grade D Particies, ‘temperature and humidity Vertiation| Tndirect [N/A Trelude production area and. impact ‘growing, and process automation, Corridors (pressure in Grade 0. corridor minimizes cross ‘contamination between processing rooms). Sanitization is performedVentiaton | NN No impact | WA Tacude, Laboratories, First and Change automation, Santiztion are made enc 9c Ventiation [NW Wa Tmpae WR Tacude ele rooms, VAC and rooms, administration autometion, sffces, canteen, one locker Nc= Admin rooms and tity rooms Administration FF/ FF/Sprinklin | N N ‘No impact | N/A ‘No impact to product quality Sprinkling | ¢ ‘istribution Tivaraulie [Tap water [WW No impact | Wa Te apes product auaity Sewage 0 Wo impat [WA Te Tact to produc ously ‘Temperature, Humidity, Light Level and Pressure