GlaxoSmithKline - Cairo ‘Appendix 5 to SOP TO 524/04 RISK IDENTIFICATION AND ASSESSMENT FORM Page tof Date Raised: 28/12/2008 Date Registered: —/-12010 Risk Unique No.: RSK— RISK OWNER DETAILS. Name: Alaa Abcel-Mohsen | Job Title: Production N-Lactam Mgr. | Department: N-Lactam Production SECTION I: DETAILS OF RISK IDENTIFICATION To be completed by Risk Owner RISK Title: ineuae tt pec and clear of task Excipients transferred into production area in their original outer wrapping (paper) Risk Description: Describe cleary the risk stuaten and the scope ofthe ick (areas. ystems, processes, predcis.) What might 99 wrong, how, where, wen .? Excipients transferred into production area in their orginal outer wrapping (paper). Is this risk: WeExisting Risic Yes ~~ G Potential Risk | Ince terone for your hoes Fet_GSK Technical Team Vist Oct 19,2009 _| Ret Background Information: descibeihe deta setnd seing or censoring tis proton erik Sale acs, orotate et sump te sk ‘+ Materials are weighed in campaign for large baich size product. + Its agreed that the process will be very hard for emptying all this quantities under laminar flow of weighing booth. ‘+ This wil lead to dust emission & blocking of HEBA fiers & also doubling time of weighing operations. ‘+ Materials delivered in its criginal containers under control of manufacturing operations, where they transferred to Incidents: N/A, Excipients (Lactose Avicel, Starch,ete...)a°s— Gaps against standards or requirements: All material Audit observation: stach ference au @u O13 a4 Other tools used in identification: seeciy ana lerence Rect cause anajssrasled lo ool, procedures and mantoriog fechnlel Vist Summary Out 09 SECTION Il: DETAILS OF RISK ASSESSMENT To be completed by Risk Owner Existing Controls: sto a1 apated contr measur tht might decrease te Inpaaliocsunence ofthe Heke the relevant monlorngprosedres oF hee cons ‘+ Materials delivered & stored outside manufacturing rooms. ‘+ Materials checked & carefully cleaned before transfer to manufacturing room's air lock, ‘© Materials transferred to other plastic containers lined with double polyethylene bags before entrance. +__Only hard containers are approved to enter manufacturing rooms & transferred directly to destruction area after used. Impact of the risk: Select aif possibile impacts ofthe risk and wiat specific | Probability of the What are tre probabiltyiehances inat the ‘msds mig edo mearh dnenton sutea nasents happen? Product Quality and Compliance: Ref. Statement from risk ‘Ci Repatition: An indent mig happen every 1-5 years ee Tl Frequency: Tine mens bomoen oosumences 7 Environment, Health & Safety Ci Business: Time, Cost, Supply Proposed risk scoring: Consequence: --2~ Likelihood: -- | Risk (index Value: ~ Risk Owner Signature: Alaa Abdel-Mohsen Area/Process Owner Approval: Alaa Abdel-Mohsen Date: 26/12/2009 Date:_28/12/2008 SECTION Ill: DETAILS OF RISK APPROVAL To be completed by Risk Team or RMCB Agreed risk scoring: ‘Consequence: Likelihood: | — | Risk Index Value: | Proposed Risk Treatment: ‘Comments: The RT agreed ‘The RMCB agreed about assessment details and scoring on Date: 25/03/2009GlaxoSmithKline Appendix 8 to SOP TO 524/06 Page | of 4 RISK STP Division - Initiating Site: GMS - Giza Site 7 ‘The primary tablets filling process does not comply with GMP Risk Titl _| standaras | Risk Identity Number: R-11367 (Internal No. RGO11) | STP No./Version: G011/01 Date: 19/10/2010 Planned date of closure: March, 2013 ‘Author, Risk Owner (RO): Elhamy Kamal Mitigation Plan Owner (MPO): | Alga Abdel Mohsen Risk Category: Product Quality CCR Number: NA i 7 Consequence | Likelihood Risk Score Risk Risk Evaluation 7 7 on epaaaat Current RIV 3 3 9 Current RIV Expected MIV 1 2 2 Expected MIV Note: The currant RIV was determined based on the expected consequence of having higher than usual customer complaints (moderate, score:2) that might happen every 1-5 yeers (possible iketnoad, score: 2). ‘The expected MIV was determined, after completing the proposed miigation plans, that the miigated consequence would be that the procuct affected remains under GSK contro! insignificant, score 1) that might rape every 5-10 years (unlikely, score: 2) STP Approval Name Signature Date Risk Owner: Elhamy Kamal Mitigation Plan Owner: | Alaa Abdel Mohsen Approval: Senior Manager: Elhamy Kamal Egypt Deputy & Operational Director: _| S2mi Michel Egypt GMS Lead: lan HoldstockGlaxoSmithKline Appendix 8 to SOP TO 524/06 Page 2 of 4 SITUATION a Problem Statement ‘The process of primary tablet filling in Non-Lactam area does not comply with the GMP requirements due to manual handling of tablets leading to possible defects in the packed product, beside potential safety issues resulting from exposure of working operators to the dust of the product even if wearing PPE Background Note: Before 2009, the primary filing of Quibron SR tablets was conducted using @ semi counter by operators that were not dedicated to the area. wutomated tablet Starting 2009, the commercial demand of the product has significantly increased, so that the productivity of the existing tablet counter could not fulfll it. So, a decision was taken to increase the productivity by manual filing of the product and in Jan 2009 five operators were hired and trained to camry out the task. One year ago, another seven outsourced operators were introduced into the process coached by the experienced operators. In Feb 2010, a Gemba was conducted on the area that showed some deficiencies against GMP and EHS requirements and proposed some corrective actions: = Qualifying the operators for the filing process and any extra operators giving hand. = GMP training for the whole operation concept ~ Label control and identification for every item and data in the room - Anew method for packing fled bottles in the basket is to be developed The following measures are currently applied as contfols to the process till completion of the proposed mitigation plans: = In Process Control checks = 100% visual inspection of filed bottles = Random checks on the area by the Production By Sep 2010, the following actions have been completed as a part of mitigation of this risk till completion of the proposed mitigation activities: ~ Improve labeling of items inside the area - Packing tablets bottles in the baskets is done in a way maintaining the integrity of the tablets inside botties and ensuring the right count of the bottles is achieved in each basket ~ Issue URB for the a new automatic tablet filing machine and getting offers regarding specified requirements, - One offer was selected for approval a Root Causes Ref Root Gause Category | RCO% | Lack of supervision from operators in the area People R602 | inadequale training to oulsourced operators working in the area regarding GMP & EHS_| People RCO3 | The manual filing is a dust generating process, Process 2 Specify the risk of doing nothing "Major finding during regulatory inspections = Receiving frequent customer complaints + Allergic or sensitisation reactions to operatorsGlaxoSmithKline Appendix 8 TARGET a Ideal solution specification = Tackle the identified root causes * Comply with GMP and EHS standards + Sustainable and prevent recurrence + Achievable within acceptable timeframe Avoid regulatory findings Eliminate customer complaints a Benefits * Secure operator safety Regular Gemba Land L2 audits, a Ongoing monitoring = Escalation to site Quality Council PROPOSED PLAN a Options to SOP TO 524/06 Page 3 of 4 = Apply adequate controls on the manual processing and ensure operator training = Replace the manual filing process with automated filling machine * Both options will be implemented @ Plans (preferably stated as mitigation plans) ‘ Tat —T Goncume Ret. Mitigation Plan Descriotion vaguen Per | canptaton | RR Tony eloquat conte one ranuad " + | Ree ateaane conv on Temanue [Alaa abcel onsen | Dee a0t0 | ROOK, Roe Replace the ara ig crocess wi eae | 2__| Replace the manual ing ‘Alga Abdel Mohsen | arch 2013 | ROOS * Refer to the detailed action plans below: Mitigation Plan No. 1: What (Action Plan) Who when Prova Vas cleaner to be used fequenty Tin HS GEBSS | "Alaa Abdel WEA [Nov 2010 improve tho clearance and earn proceduros of te area Alse Abdel Monser_| Deo 2010 [Continuous montorng and supervision of ie manual llg SUWMIeS —[-Alag Andel Monser”_| es 2010 [Conc Job Functon taining othe supers Hla Abdel Monsen | Dee 2010 fofal engioyees in thea ils Abdel Moser | ——Dse 2070 Mitigation Plan No. 2: What (ction Plan) Who Wen [seus apd angie PAR Tocnew euimmated ba Wing aching Aimed esa Tan 201 Purchase oer for new avtoeated tablet fling machine Halen Salen] [Feb 2012 Redesign the fing area fo su fhe ivoducon ofa aulomaiod Ming Ine| —Almmed essa —[ Meh 2012 fopove he now cost Hiaa Abdel Monsen” | Ap 2072 Execute he new design ‘afte isa ‘Augz0t2 Reesve and instal he ne aoiated lables ina machine Tigh, Abde-Gell—[~Nov 2012 [ually the ney isialed automated tbls ling mache Woharned Skouksy- [eb 2013GlaxoSmithKline Appendix 8 to SOP TO 524/06 Page 4 of 4 a Resources Costs and Budget required > Costs: None 5 Budget: will be determined as a part of actions that will be implemented under mitigation plan 2 Other Resources Required > HR: None > Systems: None