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Presentation Overview1) Introduction                                     1 min2) Vertical Take off                        ...
1.0 Introduction - Robert Beall                             Hometown: Syracuse, NY                             Home:      ...
2. Technology Transfer Success • Successful technology transfer will depend   on your ability to deploy these patterns of ...
2. Typical Take-Off CurvePerformance               Process Go-Live                                              Secondary ...
2. The Concept of Vertical Take-OffPerformance               Process Go-Live                                              ...
2. The Value of Vertical Take-OffPerformance               Process Go-Live                                                ...
3) Process transfers vs. Technology transfersProcess Transfer is the transfer of process information, or capability, assoc...
3) Technology Transfers vs. Process TransfersA) Process Transfer examples                   B) Technology Transfer example...
3) Technology Transfers vs. Process TransfersOPINA Process TransferProject Objective – Consolidate North American pharmace...
3) Technology Transfers vs. Process TransfersSPIRIVA Technology TransferProject Objective – Create redundant US production...
4) Technology Transfer DeliverablesIn order to specify or to document the results of the technology transfer in a flexible...
5) Application Techniques for Technology Transfers        9 Gate Technology Transfer Approach                             ...
5) Application Techniques for Technology TransfersGate 1. Project Charter -Scope of Transfer Process Project Recommendatio...
5) Application Techniques for Technology TransfersGate 1. Project Recommendation -Scope of Transfer Process The Master Doc...
5) Application Techniques for Technology TransfersGate 1. Gate 1. Project Recommendation –Know what you aretransferring.  ...
5) Application Techniques for Technology TransfersGate 1. Project Recommendation –Know what you are transferringvs. Compan...
5) Application Techniques for Technology TransfersGate 2. Project GoIn order to support the documentation of the decision ...
5) Application Techniques for Technology TransfersGate 3. Project PlanThe checklist Activities (CLA) contains a proposal r...
5) Application Techniques for Technology TransfersGate 3. Project Plan In order to specify the product transfer, the ‘Prod...
5) Application Techniques for Technology TransfersGate 3. Project PlanMS Project serves as standard tool for the project p...
5) Application Techniques for Technology Transfers                                                                        ...
5) Application Techniques for Technology TransfersGate 4. CPP / CQA Matrix                             Formulation        ...
5) Application Techniques for Technology TransfersGate 5. QC Documents Completed QC Documentation must be set prior to pro...
5) Application Techniques for Technology TransfersGate 5. QC Documents CompletedThe technology transfer products starts wi...
5) Application Techniques for Technology TransfersGate 5. QC Documents CompletedThe ‘Part 2’ of the ‘Technology Laboratory...
5) Application Techniques for Technology TransfersGate 6. Expansion Documents Completed               Specify ...         ...
5) Application Techniques for Technology TransfersGate 6. Expansion Documents Completed The technology related part of the...
5) Application Techniques for Technology TransfersGate 6. Expansion Equivalency Check                      Knowledge      ...
5) Application Techniques for Technology TransfersGate 6. Expansion Equivalency Check The equivalency check has to be cond...
5) Application Techniques for Technology TransfersGate 7. Expansion Completed               Specify ...                   ...
5) Application Techniques for Technology TransfersGate 8. Validation / Stability 1) Never fail validation / stability batc...
5) Application Techniques for Technology TransfersGate 8. Validation / Stability 1) Never fail validation / stability batc...
5) Application Techniques for Technology Transfers Gate 9 Post Approval Assessment / Post Mortem 1.   Review deliverables ...
6) Technology transfer skill setsManagement, Safety, QA, QC, Finance, Change Management, Engineering, Micro, Validations,O...
Questions?Confidential                36
Reference Sources•   *Sources:•   “Project Management Best-Practice Report”, APQC, 2004•   “A Guide to the Project Managem...
Conclusion                         In Compliance                                +                          On Schedule    ...
Product Design Attribute (PDA) TABLES                                                                                     ...
Confidential   40
5) Technology Transfer Skill Sets  Confidential                      41
3) Process transfers vs. Technology transfersTrouble -Typically both process transfers and technology transfer projects ge...
Appendix A B CD     Appendix     9 Technology Transfer – Document Flow1)9 Technology Transfer –        IChC Decision (FID)...
North to Phase V Product Transfers:Project Phases / Responsibilities                               GATE 1                 ...
North to Phase V Product Transfers:Project Phases / Responsibilities                                GATE 5                ...
North to Phase V Product Transfers:Project Phases / Responsibilities                                  GATE 9              ...
3) Technology transfer deliverables  Confidential                        47
Scope of Transfer Process (1)The ‘Tech Transfer starts with a decision to transfer continues with the transfer of(document...
Confidential   49
Approach to Technology Transfer
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Approach to Technology Transfer

By Bob Beall, ProPharma Group

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Approach to Technology Transfer

  1. 1. Presentation Overview1) Introduction 1 min2) Vertical Take off 5 min3) Process Transfers vs. Technology Transfers 10 min4) Technology Transfer Deliverables 5 min5) Application Techniques for Technology Transfer 35 min6) Technology Transfer Skill Sets 10 min7) Question Answer Session 10 min Confidential 2
  2. 2. 1.0 Introduction - Robert Beall Hometown: Syracuse, NY Home: Columbus, OH Family: Denise (Wife), Günther (Son) Maren (Daughter),Calvin (Son), Olive(dog) Hobbies: Sailing, Travel, Olympic Weightlifting Education: RIT BS - Engineering BI PMI – Ingelheim, GermanyBoehringer – Ingelheim Transfer Experience1997-2000 BIRI -Columbus, OH Solids Transfer Engineer for Optimization in North America (OPINA)2000-2007 BIRI Product transfers (Mobic, Spiriva, Micardis Plus) from (BIPKG) to USA (BIRI) .2007–2010 BIPKG International transfer between Germany and India for WW distribution.2010–2011 BVL Life-Cycle product transfer of parenteral manufacturing to new facility. Confidential 3 3
  3. 3. 2. Technology Transfer Success • Successful technology transfer will depend on your ability to deploy these patterns of success within your project organization • The slides that follow describe a roadmap you can follow to optimize your project organization of technology transfer
  4. 4. 2. Typical Take-Off CurvePerformance Process Go-Live Secondary Technology Development (fixing issues) Transfer Time • Typically, a newly transferred process experiences less than optimal performance at the start. Like an out-of-tune biplane, the “take-off” is bumpy, experiencing ups and downs at the start as the receiving team/site works out the kinks of the new process and its technology. Performance ramps slowly over time, eventually achieving the desired level of performance.
  5. 5. 2. The Concept of Vertical Take-OffPerformance Process Go-Live Secondary Development Technology (fixing issues) Transfer Time • The goal of any technology transfer should be to achieve the desired level of performance quickly and smoothly. Like a jet, the new process “takes-off” at the receiving site and delivers the desired heights of performance right from the start (vertical take-off).
  6. 6. 2. The Value of Vertical Take-OffPerformance Process Go-Live Inefficiency Rework $ Low Yields Waste Slow Speeds Unplanned downtime Technology Unclear roles Transfer Time • There is a cost associated with most Technology Transfers that tends to stay hidden. The slow, bumpy ramp-up to desired performance represents cash to the business in the form of wastes, lower product yields , lost sales opportunities and slower return on investment (ROI).
  7. 7. 3) Process transfers vs. Technology transfersProcess Transfer is the transfer of process information, or capability, associatedwith process from a donor side (knowledge center) to a receptor side. The process islearned and realized by both sides and complies all the regulatory requirements interms of Efficacy, Quality and Safety.Technology Transfer, also called Transfer of Technology (TOT) is the process ofskill transferring, knowledge, technologies, methods of manufacturing, samples ofmanufacturing to ensure that scientific and technological developments areaccessible to a wider range of users who can then further develop and exploit thetechnology into new products, processes, applications, materials or services. It isclosely related to (and may arguably be considered a subset of) knowledge transfer. Confidential 8
  8. 8. 3) Technology Transfers vs. Process TransfersA) Process Transfer examples B) Technology Transfer examplesBi-Layer tablet compression for FDC API manufacturing technologyDPI encapsulation NDA Product manufacturingGamma radiation sterilization for parenteral ANDA Product transferproductsIncludes: Includes:Change control, Process Flow, URS, FDS, Process transfer plus- Strategic Plan,IOQ, PQ, Cleaning validation, PV, Training, Validation master plan, DocumentSOP’s matrix, Supply chain planning, Method transfer, PDA, CPP,OPINA SPIRIVA- Two process train transfers every weekend - One transfer 5 years Confidential 9
  9. 9. 3) Technology Transfers vs. Process TransfersOPINA Process TransferProject Objective – Consolidate North American pharmaceutical processing in 1 plantSpecial Boundaries- No stockpiling of inventorySolution – Transfer two process trains and ancillary equipment every weekend for 5 weekendsMethod – Dedicated transfer team developed plan for 6 months prior to execution. - Process transfer was like for like. - All non production transfer activities (training, utility installation, method transfers, RM transfers, qualification documents completed prior to transfer. - Minute by minute (micro) plan developed with video tape test runs. - Easiest transfer first. - Post mortem review of each process to fine tune for next transfer. Confidential 10
  10. 10. 3) Technology Transfers vs. Process TransfersSPIRIVA Technology TransferProject Objective – Create redundant US production facility for German blockbusterSpecial Boundaries-Process not defined, 1 billion x18 µg capsule fill.Solution – Mirror German implementation with 6 month lag.Method – Dedicated team, Clear roles and responsibilities. Confidential 11
  11. 11. 4) Technology Transfer DeliverablesIn order to specify or to document the results of the technology transfer in a flexiblemanner, a TTP or TTR could cover the technology transfer of one or all process steps 1).Required documents detailing the technology transfer are listed in the Appendix of theTTP or TTR. One AllTechnology Transfer Documentation Process Step Process StepsPrepare Technology TransferTechnology Transfer Protocol – Quality Control  () 1)Laboratory Qualification Report - Part 1 (TTLQ-Part1) Checklist Laboratory Equipment‘ (CLLE) Checklist Raw Material Specifications‘ (CLRMS) Checklist Shipping‘ (CLS) Technology Transfer Protocol – Production (TTPP)  () 1)Equivalency Report – Part 1 (TTEQ-Part1) Checklist ‘Process Equipment‘ (CLPE) Execute Technology TransferTechnology Transfer Report – Quality Control  () 1)Laboratory Qualification Report - Part 2 (TTLQ-Part2) Technology Transfer Report – Production (TTRP)  () 1)Equivalency Report – Part 2 (TTEQ-Part2) 
  12. 12. 5) Application Techniques for Technology Transfers 9 Gate Technology Transfer Approach Develop Process Initial Customer Project Assessment 1 Review 2 Project 3 Mapped with CPP 4 PlanOpportunity Project Project Project CPP with Gap Recommendation Go Plan Assessment & Proposal Approved Quality Documents Eng. / Transfer Complete Validation / Batches Commercial Quality Docs Created 5 Batch Prepare MFG Execution 7 for Validation 8 Validation. batches 9 Production Documents 6 Expansion Ready for Post-Approval Completed Documented Validation Assessment / Ready for Post Mortem Execution Milestones assessed Confidential 13
  13. 13. 5) Application Techniques for Technology TransfersGate 1. Project Charter -Scope of Transfer Process Project Recommendation includes the following components: 1) Safety assessment 2) Quality assessment 3) Financial assessment 4) Overall Timeline 5) Framework for Technical Transfer Plan 6) Defines project boundaries – What is in scope, what is out of scope 7) Risks and Opportunities identified.
  14. 14. 5) Application Techniques for Technology TransfersGate 1. Project Recommendation -Scope of Transfer Process The Master Documentation provides the framework for the transfer process. The Product Transfer Master Plan (PTMP) scope document defines the boundaries of the transfer. Specify ... Establish PTMP  • scope of transfer (process steps) • technology transfer activities and documentation • qualification & regulatory activities • release as additional manufacturer   Product Transfer Master Plan’ (PTMP)
  15. 15. 5) Application Techniques for Technology TransfersGate 1. Gate 1. Project Recommendation –Know what you aretransferring. Sending Site Process Receiving Site Process P1 Stokes Mixer P2 Stokes Mixer P1 Stokes Mixer P2 Stokes Mixer Add MCC, API, Dextrose Add MCC, API, Dextrose Add MCC, API, Dextrose Add MCC, API, Dextrose and Starch, Mix for 5 min and Starch, Mix for 5 min and Starch, Mix for 5 min and Starch, Mix for 5 min Pony Mixer Pony Mixer / Blend Cube Add P1 and P2 Add P1 and P2 – Mix for 10 min – Mix for 10 min Pony Mixer Pony Mixer / Blend Cube Add Mag Stearate Study* Add Mag Stearate – Mix for 5 min – Mix for 5 min Poly Lined Drum SS Bin Transfer Blend through #10 screen Transfer Blend through #10 screen Manesty Press Killian Press Compress 25 mg tablets Study* Compress 10 mg tablets • These processes have the same SUPAC classification per CDER • This product transfer will be filed as a CBE – 30
  16. 16. 5) Application Techniques for Technology TransfersGate 1. Project Recommendation –Know what you are transferringvs. Company Metrics Product Design Attribute (PDA) TABLES CommentCTD Metric Most Favorable Less Favorable Least Favorable Critical #P7 Number of Maximum 3 Maximum 6 Above 6 4 Worldwide (e.g. – one size clear blister of one Primary material, one size opaque blister, 2 blister (7-ct push + 10-ct peel- Packaging one size HDPE bottle) push) Configurations 2 bottles 60mL + 120mL The number of worldwide primary packaging configurations reported here is determined for each drug product dosage form and strength. Blister packaging configurations are determined by counting the different combinations of forming and lidding materials being developed with consideration of the sealing area and perforations. Although the number of tablets per blister is not considered when determining the number of worldwide primary packaging configurations being developed, this aspect must be evaluated and taken into consideration during capacity, transfer and launch planning by Operations. Bottle packaging configurations are determined by counting the different combinations of bottles and closures, with consideration of size, product count and materials.P7 Packaging Standard HDPE bottle or standard Special moisture barrier packaging Special inert atmosphere and 2+ (Primary or PVC and/or PVDC blister suitable. needed (PVDC based materials oxygen barrier packaging protective inadequate) or if hygroscopic required. Novel packaging secondary or formulation prone to major failure materials required not functional after HDPE bottle opened or failure commonly used for having impact if bottle not reclosed in-use. pharmaceutical products. on product Special light protective packaging Materials not approved for quality) needed (lined bottles or dark glass). use in food or drug Special design or configuration of packaging in US or EU. HDPE bottles (e.g. desiccant), Polypropylene bottle, or Aluminum blister, bag, overwrap required. Multiple suppliers available. Only single supplier available but Single source supply with 5+ other suppliers can be developed. patent restrictions against Blister foils: Alcan + Constantia Bottle: Gap last alternate suppliers.
  17. 17. 5) Application Techniques for Technology TransfersGate 2. Project GoIn order to support the documentation of the decision to execute technicaltransfer the – Decision template specifies format and content. Technology Transfer Template eRoom Folder: 1 Transfer Management 18/102 January 17, 2007 Handbook for Transfers of Chemical Products V02
  18. 18. 5) Application Techniques for Technology TransfersGate 3. Project PlanThe checklist Activities (CLA) contains a proposal regarding activities which are inprinciple relevant for a transfer. Relevant activities can be marked and copied to theproject plan. Transfer of Chemical Product - Checklist Activites Process Step GL Activity Start Date End Date Resp. Rel. Example Set-up Transfer 2 Set up transfer project PL yes Set-up Transfer 2 Set up eRoom PL yes Set-up Transfer 2 Denominate transfer team PL yes Set-up Transfer 2 Prepare kick-off meeting PL yes Preparation of TTP 2 Idemtification of documents PM RU yes Preparation of TTP 2 Preparation of documents PM SU yes Preparation of TTP 2 Preparation of TTP - Quality Control QC SU yes Acquisition and evaluation of the existing documentation on the synthetic Preparation of TTP 2 P SU yes method, including eventual batch records Acquisition and evaluation of general documentation about ritical Preparation of TTP 2 P SU yes parameters or of a complete development report Preparation of TTP 2 Check production needs and their compatibility with the actual planning P SU yes Preparation of TTP 2 Feasibility analysis in plant on the existing documentation and lay-out hypothesis of the process P RU eRoom Folder: yes Preparation of TTP 2 Cost analysis on production hypothesis PM RU 1 Transfer Management yes Acquisition and evaluation of the safety documentation of the process, Preparation of TTP 2 P RU yes including MSDS
  19. 19. 5) Application Techniques for Technology TransfersGate 3. Project Plan In order to specify the product transfer, the ‘Product Transfer Master Plan’ (PTMP) template provides predefined structure, format and content. Template eRoom Folder: 2 Tech Transfer
  20. 20. 5) Application Techniques for Technology TransfersGate 3. Project PlanMS Project serves as standard tool for the project planning of the product transfer. Inorder to accelerate the preparation of the project plan, tasks from the activity list couldbe pasted in. Example eRoom Folder: 1 Project Management
  21. 21. 5) Application Techniques for Technology Transfers Conduct the Pre-Use Flush for the Closed Solvent TransferGate 4. Process Flow System Sequential or parallel? 1) Map production process with SME / Operators 2) Identify Critical Process Parameters (CPP) and Critical Ensure vent bungholes on both metal waste drum and Ensure proper bonding and grounding of equipment. Where described solvent drum Quality Attributes (CQA) as they relate to finished are open product not ok ok ok not ok 3) Confirm all CPP / CQA have studies to support acceptance ranges. open them Do I need to 4) Conduct studies to confirm CPP / CQA ranges to fill contact supervisor first? Attach Inlet hose and Valve No.2 of CST system to the gaps vessel and record the weight. 5) Determine best practice / gold standard process 6) Create CPP / CQA database (PANDA) 7) Compare CPP / CQA data values to “gold standard” Calculate the Calculate 95% amount of of total required Dehydrated Dehydrated Alcohol, Alcohol, USP/EP/BP to USP/EP/BP to add to the add to the and ranges to determine cause of variance. vessel via the is this formulation CST system correct? vessel (underfill?) confusing to me.. 8) Provide real time data trending to operators to enable Calculate 95% educated process adjustment. minus the Underfill Add this amount to the Continue agitation throughout solvent transfer formulation vessel. Target transfer weight of the vessel achieved Remove inlet hose and Valve No.2 from the vessel and record weight. Confidential 22
  22. 22. 5) Application Techniques for Technology TransfersGate 4. CPP / CQA Matrix Formulation Set Up Process Sub‐Step Collect  Check Room  Check  Check Tank  Equipment  Attach  Record  for  Isolator for for  and check for  Pit Check  Load  Attach  Isolator to Tare  Cleanliness Cleanliness Cleanliness Cleanliness Scale Isolator CST  tank Wt Visual, Visual Conf Set up  Logbook  Mork sheet BOM ‐ Challenge  Verify  per SOP‐ Logbook confconf Alcohol  Props /  Calibration  BOM Set up  No breach  Print tick CQA Specification Visual Conf Visual Confrinse. clamp Verify cal Integrity per SOP alarms 0.5 kg  Clear, colorless to pale yellow free from visable  Appearance Contamination 1 1 5 3 1 1 1 1 1 Volume  Not less than 16.7 mL/Vial 1 1 1 1 1 1 1 1 1 Assay 98.0% ‐ 108.0% of label 1 3 3 3 3 1 1 1 5 pH 4.0 ‐ 6.0 1 1 3 3 1 1 1 1 1 Moisture NMT 0.6% 1 3 5 5 1 1 1 2 1 NMT 0.05 AU at A420 nm  Color of solution using ethyl alcohol blank 1 1 3 1 1 1 1 1 1 Ethanol 90% ‐ 110% of labeled amt 1 1 5 1 3 1 1 1 5 Paclitaxel Products NMT  0.1% 7 Epipaclitaxel NMT 0.3% Limit of  Total Degred Products NMT  Degredation 1.0% 1 1 2 4 1 1 1 1 4 Residual Solvents USP 467 1 1 1 1 1 1 1 1 1 NMT 0.67 EU/mg of  Microbe Testing Paclitaxel 3 3 5 3 1 3 1 2 1 NMT 6,000 parts > 10 micron Particulate Matter NMT 600 parts > 25 micron 1 1 1 1 1 1 1 1 1 Based on ICH Q9 Guidelines Confidential 23
  23. 23. 5) Application Techniques for Technology TransfersGate 5. QC Documents Completed QC Documentation must be set prior to process transfer Specify ... Establish PTMP  • scope of transfer (process steps) • technology transfer activities and documentation • qualification & regulatory activities • release as additional manufacturer   Product Transfer Master Plan’ (PTMP) Quality Control Docs complete
  24. 24. 5) Application Techniques for Technology TransfersGate 5. QC Documents CompletedThe technology transfer products starts with the qualification of the laboratory (QCTransfer) and continues with the transfer of the manufacturing process (ProductionTransfer). The equivalency check of the chemical product has to be performed by theQC of the Sending Unit 1). Production Product Receiving Unit 1st step:2nd step: Qualification of laboratoryEquivalency check of (Parallel analysis of reference product substance by SU and RU)(Comparison of transfer batcheswith reference batches) Production Transfer Product Quality Control Sending Unit Transfer Quality Control Test Test Sending Unit Receiving Unit
  25. 25. 5) Application Techniques for Technology TransfersGate 5. QC Documents CompletedThe ‘Part 2’ of the ‘Technology Laboratory Qualification Report (TTLQ)’ templatesupports to record the analytical results obtained in the parallel analysis by the RU, todocument the comparison of the results and the conclusions with regard to the Examplefulfillment of the acceptance criteria. TTLQ –P2 (TTRQC relevant part) eRoom Folder: 3 Quality Control
  26. 26. 5) Application Techniques for Technology TransfersGate 6. Expansion Documents Completed Specify ... Establish PTMP  • scope of transfer (process steps) • technology transfer activities and documentation • qualification & regulatory activities • release as additional manufacturer   Product Transfer Master Plan’ (PTMP) Quality Control Prepare Docs complete Technology Transfer Docs
  27. 27. 5) Application Techniques for Technology TransfersGate 6. Expansion Documents Completed The technology related part of the transfer is documented in technology transfer documentation. Technology Transfer – Quality Control Technology Transfer - Production 1) 4)  Specify scope of QC Transfer Prepare  Specify scope of Production Transfer Prepare   TT Protocol – Quality Control (TTPQC) Define Transfer Campaign Size  Check equivalence of laboratory   TT Protocol – Production (TTPP)   CL ‘Laboratory Equipment (CLLE)  Check equivalence of process  Check raw material specifications at   CL ‘Process Equipment (CLPE)   CL ‘Raw Material Specifications’ (CLRMS) 5)  Specify equivalency check  Ship reference substances to RU   TT ‘Equivalency Qualification–Part 1’ (TTEQ-P1)   CL ‘Shipping’ (CLS)  Specify qualification of RU laboratory   TT ‘Laboratory Qualification–Part 1’ (TTLQ-P1)  Train manufacturing process at SU Execute Coach manufacturing process at RU 3)  Train analytical methods at SU Execute   CE ‘Certificate Training – Production’ (CETP)    CE ‘Certificate Training – Quality Control’  Produce transfer campaign at RU  Execute parallel analysis at RU  Execute equivalency check   TT ‘Laboratory Qualification–Part 2’ (TTLQ-P2)   TT ‘Equivalency Qualification–Part 2’ (TTEQ-P2)  Document results of QC Transfer  Document results of Production   TT Report – Quality Control (TTRQC)   TT Report –Production (TTRP) January 17, 2007
  28. 28. 5) Application Techniques for Technology TransfersGate 6. Expansion Equivalency Check Knowledge Range Proven Acceptable Range Normal Operating Range Target Value Parameter Scale
  29. 29. 5) Application Techniques for Technology TransfersGate 6. Expansion Equivalency Check The equivalency check has to be conducted for non critical parameters by min/max comparison. EXAMPLE Production SU Charts 1) have to Limit (USL) demonstrate For critical parameters QC Upper Specification be usedProduction RU equivalency. to Upper Tolerance Limit (UTL) 2) Measured Value Specification + 3 3) Sample Lower Tolerance Limit (LTL) 2) No Lower Specification Limit (LSL)Remarks: 1) – upper or upper/lower limited control chart 2) Synonym: Upper/ Lower Control Limit; 3) 99,7% of the data should lie within the tolerance limits, the probability of afalse decision is 0,3% 30 Confidential 30/102
  30. 30. 5) Application Techniques for Technology TransfersGate 7. Expansion Completed Specify ... Establish PTMP  • scope of transfer (process steps) • technology transfer activities and documentation • qualification & regulatory activities • release as additional manufacturer   Product Transfer Master Plan’ (PTMP) Quality Control Prepare Execute Docs complete Technology Transfer Docs Regulatory Activities Execute Expansion  Document ... • results of technology transfer • results of qualification and regulatory activities • release as additional manufacturer   Product Transfer Master Report’ (PTMR)
  31. 31. 5) Application Techniques for Technology TransfersGate 8. Validation / Stability 1) Never fail validation / stability batches. Highest variation
  32. 32. 5) Application Techniques for Technology TransfersGate 8. Validation / Stability 1) Never fail validation / stability batches. Degradation T @ 25°C/60% r.H. 101.0 100.5 G76757 G76972 G77267 100.0 G77989 99.5 assay T [%] 99.0 98.5 98.0 97.5 0 2 4 6 8 10 12 14 16 18 20 time [month]
  33. 33. 5) Application Techniques for Technology Transfers Gate 9 Post Approval Assessment / Post Mortem 1. Review deliverables vs. plan 2. Review budget vs. plan 3. Review timeline vs. Base Plan 4. Revise templates accordingly.
  34. 34. 6) Technology transfer skill setsManagement, Safety, QA, QC, Finance, Change Management, Engineering, Micro, Validations,Operations, Customer, Contract Management, DRARACI 35
  35. 35. Questions?Confidential 36
  36. 36. Reference Sources• *Sources:• “Project Management Best-Practice Report”, APQC, 2004• “A Guide to the Project Management Book of Knowledge®”, U.S. Department of Defense, 2003• “European Technology Transfer Guide to Best Practice”, Teurpin, 2001• “Benchmarking Best-Practices in Technology Transfer”, Colorado Institute for Technology Transfer and Implementation, 1993
  37. 37. Conclusion In Compliance + On Schedule + In Budget = SUCCESS ! ProPharma Group is the Best Choice to balance all three needs!Confidential 38
  38. 38. Product Design Attribute (PDA) TABLES Comment Critical at CTD Metric Most Favorable Less Favorable Least Favorable Milestone #P7 Number of Maximum 3 Maximum 6 Above 6 4 Worldwide (e.g. – one size clear blister of one Primary material, one size opaque blister, 2 blister (7-ct push + 10-ct peel- Packaging one size HDPE bottle) push) Configurations 2 bottles 60mL + 120mL The number of worldwide primary packaging configurations reported here is determined for each drug product dosage form and strength. Blister packaging configurations are determined by counting the different combinations of forming and lidding materials being developed with consideration of the sealing area and perforations. Although the number of tablets per blister is not considered when determining the number of worldwide primary packaging configurations being developed, this aspect must be evaluated and taken into consideration during capacity, transfer and launch planning by Operations. Bottle packaging configurations are determined by counting the different combinations of bottles and closures, with consideration of size, product count and materials.P7 Packaging Standard HDPE bottle or standard Special moisture barrier packaging Special inert atmosphere and 2+ (Primary or PVC and/or PVDC blister suitable. needed (PVDC based materials oxygen barrier packaging protective inadequate) or if hygroscopic required. Novel packaging secondary or formulation prone to major failure materials required not functional after HDPE bottle opened or commonly used for having impact failure if bottle not reclosed in-use. pharmaceutical products. on product Special light protective packaging Materials not approved for quality) needed (lined bottles or dark use in food or drug glass). Special design or packaging in US or EU. configuration of HDPE bottles (e.g. desiccant), Polypropylene bottle, or Aluminum blister, bag, overwrap required. Multiple suppliers available. Only single supplier available but Single source supply with 5+ other suppliers can be developed. patent restrictions against Blisterfoils: Alcan + Constantia Bottle: Gaplast alternate suppliers. Confidential 39
  39. 39. Confidential 40
  40. 40. 5) Technology Transfer Skill Sets Confidential 41
  41. 41. 3) Process transfers vs. Technology transfersTrouble -Typically both process transfers and technology transfer projects get intotrouble because:1) Process was not “Right the first time” before the transfer.2) Process technology was not up to date technology before transfer.3) Resolve compliance issues during transfer.Result – Extended timelines, cost overrun. Confidential 42
  42. 42. Appendix A B CD Appendix 9 Technology Transfer – Document Flow1)9 Technology Transfer – IChC Decision (FID) Product Transfer Master Plan’ (PTMP) IChC decision on Transfer of CP Specify transfer of CP Document Flow Technology Transfer Protocol –QC (TTPQC) QC Transfer Specify scope of Technology Transfer –QC Transfer –P Production Transfer Specify scope of Technology roduction Techn. Transfer Protocol Checklist Laboratory Check equivalency –Production (TTPP ) Equipment (CLLE) of laboratory Define Transfer Campaign Size Checklist Raw Material Check adequacy of raw Specifications (CLRMS) material specifications RU/SU Checklist Ship reference substances Check comparability of Checklist Process Shipping (CLS) to RU process equipment Equipment Laboratory Qualification Specify qualification Report –Part 1 (TTLQ-P1) parameters (RU laboratory) Specify equivalency Equivalency Report – check Part 1 (TTEQ-P1) Train analytical methods at SU Training Certificates (CETQC) Coach analytical methods at Train manufacturing RU (optional) process at SU Training Certificates Laboratory Qualification Execute parallel analysis (CETP) Report –Part 2 (TTLQ-P2) at RU Coach manufacturing process at RU Technology Transfer Document results of Report –QC (TTRQC) Technology Transfer - QC Produce transfer campaign at RU Equivalency Report – Execute equivalency check Part 2 (TTEQ-P2) Document results of Techn. Techn. Transfer Report Transfer - Production –P roduction (TTRP ) Qualify CP Execute Regulatory Activities Product Transfer Master Report’ (PTMR) Document transfer of CP End Remarks: CP –Chemical Product; 1) for more details please see Handbook Handbook for Transfer of Chemical Products J 17, 2008 an
  43. 43. North to Phase V Product Transfers:Project Phases / Responsibilities GATE 1 GATE 2 GATE 3 GATE 4 44
  44. 44. North to Phase V Product Transfers:Project Phases / Responsibilities GATE 5 GATE 6 GATE 7 GATE 8 45
  45. 45. North to Phase V Product Transfers:Project Phases / Responsibilities GATE 9 46
  46. 46. 3) Technology transfer deliverables Confidential 47
  47. 47. Scope of Transfer Process (1)The ‘Tech Transfer starts with a decision to transfer continues with the transfer of(documented) knowledge, the demonstration of ability of the receiving unit tomanufacture the product to the satisfaction of all involved parties and ends withsuccessfully regulatory variations and the release as additional manufacturer. Release as additional Manufacturer (End) Tech Transfer CRC Establish Product Transfer Master Application Report Execute regulatory activities ... conceptual Qualify API (by MP) Execute Technology Transfer – Production Equivalency of API MP Approval Execute Technology Transfer – QC Laboratory Qualification 1) Prepare Technology Transfer – Production Prepare Technology Transfer – QC Establish Product Transfer Master Plan Manage project ... IChC decision (Start) TimeRemarks: 1) Start of production of transfer batches; MP – Manufacturing Pharma; CRC – Change Review Committee; IChC – International 48/102 January 17, 2007Chemicals Committee Handbook for Transfers of Chemical Products V02
  48. 48. Confidential 49

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