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1、High potent OSD multi-production plant Concept, Containment & Cleaning 2015 Vogel Pharmaceutical Engineering International Forum Jun . 2015, Taizhou, ChinaHorch Guo, H Shanghai Roche Pharmaceutical Ltd.VOGELVOGEL制药业ContentPART I: CONCEPT & REGULATIONPART II: CONTAINMENTPART III: CLEANING VOGELVOGEL2
2、制药业PART I: CONCEPT & REGULATIONVOGELVOGEL3制药业API Harzard ClassificationOEB, OEL, ADE4制药业WW Market-Sharing (%)%Sales growth: CAGR 2013-202012%8 %4 %0 %-4 %0 %4 %8 %12 %16 %OncologyAnti-diabeticsAnti-Virus VaccinesSensory OrgansDermatologicalMS therapiesAnti-rheumaticAnti-hypertensiveBronchodilatorsSo
3、urce: Evaluatepharm World Preview 2014, Outlook to 2020TOP10 Therapy area in Y2020Market share & Sales Growth for hipo5制药业VOGELVOGEL6World TierState TierOrganization TierCompany & Peers TierRegulations & GuidelineHierarchy 制药业VOGELVOGEL7Regulations & GuidelineCross-contaminationAuthoritiesChapters/G
4、uidelinesKey pointsSFDAChapter 4, Premises & Facilities, Article 46, Article 53Cross-contamination and dedicated facilities requirements on layout, premises , Penicillins and other beta lactam antibiotics Chapter 9, Production Management, Article 197, 198Measures to avoid the cross- contaminationsWH
5、OTRS 961, 2011,Annex 5Non-Sterile HVACTRS 957, 2010, Annex 3 GMP for hazard productsEMAV4, Chapter 3, Premises & Equipment, Mar, 2015Section 6V4,Chapter 5, Production, Mar 2015 Section 1721FDAICH Q7 4.4, 21 CFR 211.42 Penicillins and other beta lactam antibiotics Guidance for Industry - Non-penicill
6、in Beta-Lactam drugs, April 2013 Framework for Preventing Cross- Contamination ICH Q7 4.4, 21 CFR 211.42high pharmacologic activity or toxicity products制药业8GMP Inspection StatisticsPIC/S top most severe GMP deficiencies Design and maintenance of premisesContamination, potential for (chemical, physic
7、al, microbial)Design and maintenance of equipmentSterility assuranceBatch release procedureProcess ValidationCleaning ValidationInvestigation of anomaliesDocumentation-QS elements/procedureRegulatory issuesDocumentation-manufacturing制药业VOGELVOGELPoor Quality& incompliance results9制药业PART II: CONTAIN
8、MENTVOGELVOGEL10制药业High potent OSD plant Containment -Containment Levels11Secondary Containment-HVAC 100% fresh air -PAL, MAL, De-con ALPrimary ContainmentProductPersonnel-Equipment tightness -Negative Pressure -Transfer Container -Cleaning procedure -Dust collection-PPE -Half Suit -Full Suit -Breat
9、hing Air制药业High potent OSD plant Containment -Product containment Risk -Classical12制药业High potent OSD plant Containment -Improvement based on the Risk State-of-art13制药业High potent OSD plant Containment Example:Tablet Press System14VOGELVOGEL制药业High potent OSD plant Containment -Briefly Comparision H
10、ipo vs. Lopo OSD plant in MNCProcess EquipmentsHigh PotentLow PotentFacilities/UtilitiesOperation expense CAPEXOPEXMaintenance EngineeringFacilities/ UtilitiesQuality cost15EHSStartup制药业Primary Containment-Design Phase -Encapsulation16VOGELVOGEL制药业Primary Containment -FAT ,SAT phase/ Surrogate Testi
11、ngSurrogatePositivesNegativesTypical ApplicationsLactose-Low toxicity -Low cost -Water soluble -Non API-Agglomeration -Relatively difficult analysis-Not as effective for comparison to extremely dusty materials. -Widely used in FATNaproxen-Na-Extremely dusty -Low toxicity -Simple analytical method -H
12、ighly water soluble -For all process-GMP cleaning issues after testing -Relatively expensive-Very useful for testing of systems with highly hazardous -Widely used in SAT/OQParacetamol-Reasonably dusty -Multiple analytical methods -Water soluble-GMP cleaning issues after testing-Easier to analyze tha
13、n lactose -Used also in SAT/OQ17Source: ISPE Good Practice Guide: -Assessing the Particulate Containment Performance of Pharmaceutical Equipment, 2ndversion. VOGELVOGEL制药业Primary Containment -FAT phase/ Surrogate Testing-Lactose18VOGELVOGEL制药业Secondary Containment Process Room Mode l Non high potent
14、 API -Negative Pressure -System closure control-High risk for multi- production if primary containment failed-Low reliable for the cleaning corridor19VOGELVOGEL制药业Secondary Containment-Process Room Model /Non hipo API improvements-Cascade Negative Pressure control with MAL & PAL- System closure cont
15、rol-Higher risk if the primary & seconday containment failed -Mild reliable for the cleaning corridor20VOGELVOGEL制药业Secondary Containment-Process Room Model /High potent API-Cascade Negative Pressure control with MAL & PAL-De-contamination locker for clean Person Flow even with contamination- System
16、 closure control-High reliable Clean corridor-Low risk for the multi-production21VOGELVOGEL制药业Secondary Containment-HVAC-100% fresh air22VOGELVOGEL制药业HiPo OSD Plant- Layout Model -Horizontal Layout for integrated systems23ProcessUtilities-Hipo multi-production plant -Process Room Modular design with PAL, MAL and De-com AL.-Seperated Process & util
