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1 Outsourcing: Pitfalls and Best Practices IQPC Contract Manufacturing Forum Paul Woitach Pharmaceutical Advisors, LLC Pharmaceutical Advisors, LLC 316.

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Presentation on theme: "1 Outsourcing: Pitfalls and Best Practices IQPC Contract Manufacturing Forum Paul Woitach Pharmaceutical Advisors, LLC Pharmaceutical Advisors, LLC 316."— Presentation transcript:

1 1 Outsourcing: Pitfalls and Best Practices IQPC Contract Manufacturing Forum Paul Woitach Pharmaceutical Advisors, LLC Pharmaceutical Advisors, LLC 316 Wall Street, Second Floor Princeton, NJ May 24, 2006

2 2 Key Principles for Success Plan Backwards from LaunchPlan Backwards from Launch Integrated ViewIntegrated View Think Tech Transfer EarlyThink Tech Transfer Early Think Quality Agreements EarlyThink Quality Agreements Early Structure and Manage Vendor RelationshipsStructure and Manage Vendor Relationships Staff appropriately for OutsourcingStaff appropriately for Outsourcing Thats all motherhood and apple pie! Whats actionable????

3 3 Can You Hear The Train Coming? We dont need to think about that because were going to license out in Phase II…We dont need to think about that because were going to license out in Phase II… Our licensing partner will worry about that…Our licensing partner will worry about that… Lets just get GMP material for everything…Lets just get GMP material for everything… Well get a consultant to write the CMC section when the time comes…Well get a consultant to write the CMC section when the time comes… Were starting to work on our Quality Manual…Were starting to work on our Quality Manual… Its too early to be thinking about a Quality Agreement – its just development work…Its too early to be thinking about a Quality Agreement – its just development work…

4 4 Management View of the Timeline NominationPhIPhIIPhIIINDA/MAAApproval License? DP Activities Preclinical Phase I Phase II Phase III Launch API API Activities Drug Product

5 5 A Truer Picture NominationPhIPhIIPhIIINDA/MAAApproval Launch API/DP Enabling Technology & Supply Manufacturer API/DP Technology/Supplies RMAPIDP PhIII Supplies RMAPIDP Launch Planning RMDPDP StabilityAPI PAIn Planning RMAPIDP ICH Stability ICH DP Stability Planning DP Technology API Technology Raw Materials API Activities DP Activities Enabling Evolving API & Drug Product Demand

6 6 As You Plan CMO Relationships… You should be considering: Final FormFinal Form Synthesis technology Interim and preferred bond forming routeSynthesis technology Interim and preferred bond forming route Analytical TechnologyAnalytical Technology –Raws –Intermediates and in process controls Process Development & OptimizationProcess Development & Optimization Process safety & reaction engineeringProcess safety & reaction engineering Preferred Salt, polymorph, solvate – what & whenPreferred Salt, polymorph, solvate – what & when cGMP needs & timingcGMP needs & timing –Clinical and safety demands –Dosage form development demands Demonstration of manufacturing including robustness & scalabilityDemonstration of manufacturing including robustness & scalability Trade off between speed and process learningTrade off between speed and process learning Reproducibility of bulk form & qualityReproducibility of bulk form & quality Documents – Regulatory & Tech TransferDocuments – Regulatory & Tech Transfer Sourcing strategies & ability to manage distanceSourcing strategies & ability to manage distance Vendor management & staffingVendor management & staffing Most enter contract manufacturing relationships without adequate consideration

7 7 Advisors Functional Focus Integrating Research, Development, Engineering and Commercialization Expertise Supporting Development, Operations, Strategy and Portfolio Management Rapid, Interactive Expert Panels Rapid, Interactive Expert Panels Practical Quality Systems & Regulatory Practical Quality Systems & Regulatory Resolve Issues Build Skills Chemistry, Formulation Drug Delivery Safety & Efficacy ADME Resolve Issues Build Skills Chemistry, Formulation Drug Delivery Safety & Efficacy ADME Integrated Development View Linking CMC, Tox, Clinical Integrated Development View Linking CMC, Tox, Clinical Portfolio Decisions, Due Diligence & Valuation Portfolio Decisions, Due Diligence & Valuation Scale-up & Sourcing Decisions Scale-up & Sourcing Decisions Operational Input to Capital Plans Operational Input to Capital Plans

8 8 Inverting the Consulting Model… Proven Delivery Insight-Driven Customized Resourcing Integrated, Experienced Functional Perspective Hands-On Problem-Solvers Cost-effective, Flexible, Independent Industry Experts ExperiencedConsultantManagers Unique Client Situation Situation

9 9 Objective & Approach Meeting ObjectivesMeeting Objectives –Provide useful tips & tools to help you anticipate and succeed –Capitalize on our experience ApproachApproach –Best & Worst practices fall into two groupings 1.Planning & Requirements Definition 2.Staffing, Execution & Managing the Relationship –Checklist approach –Examples

10 10 Planning & Requirements Definition Registration strategyRegistration strategy Integration of DS & DP plansIntegration of DS & DP plans Timing and Quality of tech transfer packageTiming and Quality of tech transfer package Early definition of information needsEarly definition of information needs Integrated understanding of scale-up AND Tech Transfer capabilityIntegrated understanding of scale-up AND Tech Transfer capability Unrealistic flexibility expectationsUnrealistic flexibility expectations Contingency planningContingency planning

11 11 Execution & Managing the Relationship Adequate resourcesAdequate resources Managing & metricsManaging & metrics Expecting vendors to be critical and help you avoid mistakesExpecting vendors to be critical and help you avoid mistakes Quality Agreement timing & specificityQuality Agreement timing & specificity Process data & understandingProcess data & understanding

12 12 Tech Transfer Package Package ElementsPackage Elements –Technology –Raw Material specs & vendors –Unit Operations as practiced –Mass Balance as complete as possible –General safety and environmental –Analytical Requirements –Proposed specs for API Useful for make vs. buy decisionsUseful for make vs. buy decisions Gives vendor an adequate viewGives vendor an adequate view –Help them understand their risk –Typically big ROI – can avoid cost/risk premiums –Reduces ifs and thens in their proposed scope –Avoids excessive go-no-go steps Enable Efficient & Credible Interaction and Decisions

13 13 Early Definition of Info Needs Buying chemistry AND informationBuying chemistry AND information To PAI, RegistrationTo PAI, Registration Establish a documentation system for all contractorsEstablish a documentation system for all contractors Specify what you want and how you want it documentedSpecify what you want and how you want it documented –Beyond just batch tickets Will the resources be available to get all the analytical work done that you will need?Will the resources be available to get all the analytical work done that you will need? Build a Development Report as you goBuild a Development Report as you go Demonstrate professionalism and competence to contractors and your regulatory teamDemonstrate professionalism and competence to contractors and your regulatory team Lower Costs and Avoid Rework / Wasted Effort

14 14 Scale-up & Tech Transfer Capability Can scale up on time but…Can scale up on time but… –Will the way they scale-up processes be easily transferable to another facility? –Or are they best at scaling up for their equipment? –Does their scale-up plan favor use of their technology –To what stage can development vendor support your needs? –Do you know when you need to lock the process for ICH? –If needed, do you know when you need to confirm and qualify a commercial CMO? –Less Tech transfers can be better but know the trade-offs Very Few One Stop Shops Work Back from Launch and know what you need, when

15 15 Registration Strategy Selection of Registered Starting MaterialSelection of Registered Starting Material –True requirements for strict optimization, process validation and rigorous analytical control –Flexibility in commercial scale decisions Impact on out licensing valueImpact on out licensing value –Future filing and sourcing flexibility Impact on cost & time for sponsorImpact on cost & time for sponsor What stability position should you plan for?What stability position should you plan for? Earlier Decisions Provide Critical Enabling Direction

16 16 Process Data & Understanding Affects ability to manage in an outsourced environmentAffects ability to manage in an outsourced environment Enables informed decisions on key trade-offsEnables informed decisions on key trade-offs –Speed of Phase I supply Costlier, slower scale-up & process developmentCostlier, slower scale-up & process development –Early investment in analytics & technology Slower initial supplySlower initial supply –Do you know enough to bet on all doing DP work under GMP to speed time into man? Technology infoTechnology info Supply & demand infoSupply & demand info Scale and Quantity definition for your vendor so they can help youScale and Quantity definition for your vendor so they can help you –When to seek multiple runs at given scale –When to race to scale-up –How to apply simulation technologies –How to determine ROI –Inputs needed to make these decisions –Do you know when you need to lock the process for ICH? FMEAFMEA Ability to learn from failuresAbility to learn from failures All affect vendor selection, vendor ability to deliver and the robustness of your process and data package

17 17 Unrealistic Flexibility Expectations The best vendors dont have much flexibilityThe best vendors dont have much flexibility –Be wary of too much! Contracting and scheduling lead timesContracting and scheduling lead times –Hedge rules of thumb & big pharma perspectives 3- 6 months for contractor identification and selection3- 6 months for contractor identification and selection Build in scheduling lead-times for when problems occurBuild in scheduling lead-times for when problems occur Build in iterations for to-be-demonstrated technologyBuild in iterations for to-be-demonstrated technology Only certainty is that things will go wrongOnly certainty is that things will go wrong Understand where theres leverage and where vendors situation can affect youUnderstand where theres leverage and where vendors situation can affect you Realistic Timelines and Risks

18 18 Adequate Resources On-site involvement early in relationshipOn-site involvement early in relationship –More time on-site up front, less time fixing things later –Proactive vs. Reactive –In-person builds relationship & personal commitment Over / under importance of geography & distanceOver / under importance of geography & distance Central Project management and information flowCentral Project management and information flow –Be easy to do business with –Do not impede scientist-to-scientist interaction when needed It Takes Resources BUT…It Enables Alignment Efficiency

19 19 Integration of DS & DP Plans EarlyEarly –Analytical methods - DS, DP or other activity Salt Selection – DP activitySalt Selection – DP activity Chemistry supply – DS ActivityChemistry supply – DS Activity Avoid delay because DS or DP vendor has to waitAvoid delay because DS or DP vendor has to wait –Will raws be available to make what you need when you need it –Understand Bioavability early DP TimelineDP Timeline Quantity of APIQuantity of API LaterLater –Feedback between DS & DP Development –Avoid scope changes & unrealistic demand to make up for lost time DelaysDelays Erosion of vendor relationshipErosion of vendor relationship –Timing of Polymorph study vs. risk –Will raws be available to make what you need when you need it Dont Rely on Vendors to Integrate For You

20 20 Managing & Metrics Dont assume vendor is motivated to deliver You are one of many clientsDont assume vendor is motivated to deliver You are one of many clients –Understand how they get their bonus Are they motivates to help you achieve your goals?Are they motivates to help you achieve your goals? Keep it simpleKeep it simple Dont confuse speed with on-timeDont confuse speed with on-time Understand how your demands change as you progressUnderstand how your demands change as you progress Put in the effort to be a good clientPut in the effort to be a good client Inspect What You Expect

21 21 Expecting Vendors to be Critical CMOs are a service businessCMOs are a service business –Focus on doing what customers ask them to do –Dont expect them to stop you from making mistakes How many vendors get a bad reputation for telling their clients what the client needs?How many vendors get a bad reputation for telling their clients what the client needs? –Will they stop you from making process changes that affect impurity profiles? Its Your Development Plan

22 22 Quality Agreements I Inadequate Specificity Raw MaterialsRaw Materials –Change in impurity provide because vendor switched RM supplier Communications of Deviations & InvestigationsCommunications of Deviations & Investigations –Delayed investigation of unexplained variation cost $750K to fix –Metabolic conditions ( low DO2) and RM changes altered fermentation –Vendor was operating within its agreement Documentation to support filingsDocumentation to support filings –Inadequate documentation resulted in re-work Vendor was meeting specs agreed toVendor was meeting specs agreed to Company had not thought through filing requirementsCompany had not thought through filing requirements –Site specific and product specific post-run data check lists –Get what you need –Avoid cost and delay of back and forth –Taxes your scarce resources and busts timeline Not Spelling Things Out Can Create Big Risks Later

23 23 Quality Agreements II Too much specificity Define WHAT you need but allow the vendor to propose HOWDefine WHAT you need but allow the vendor to propose HOW –Avoid unnecessary rigor and scope –Allow for vendors systems Consider how Quality Agreements differ for development work and for supplyConsider how Quality Agreements differ for development work and for supply Careful about applying consultant templatesCareful about applying consultant templates QA audit TeamQA audit Team –Operational AND Quality considerations –Consider ability to manage ongoing –What some can manage, others can not One of the Key Elements You Should Control

24 24 Eliminating a Bottleneck Summarize Ratings against criteria Narrow down to 2- 3 potential suppliers Review with internal stakeholders Recommendation and approval of at least 2 Final negotiations and initial contracting Contingency Plan Supplier Preferences Long-List to Short List Execute CDA Request for Information (RFI) on capability areas of interest Remote / Paper Quality Audit Initial site / technical visit Begin business evaluation Establish selection criteria External Input Capacity Performance Request For Proposal (RFP) Draft workscope Share desired Terms & Conditions (T&Cs) and Quality Agreement (QA) Establish selection criteria Tech Transfer package Pre-Selection Technical Assessment Preliminary Quality review and criteria for Quality Audit Preliminary negotiation Price T&Cs Quality Agreement Capacity Performance Quality Audit Identify potential issues related to Quality Agreement Before or in parallel with Contracting QA Sign-off Quality Agreement PO/Final sign off Kick-off Contracting Finalization Negotiation & Contracting Finalize workscope document Finalize price QA OK – Internal Taking action earlier to support tight timelines

25 25 Summary Plan Backwards from LaunchPlan Backwards from Launch Integrated ViewIntegrated View Think Tech Transfer EarlyThink Tech Transfer Early Think Quality Agreements EarlyThink Quality Agreements Early Structure and Manage Vendor RelationshipsStructure and Manage Vendor Relationships Staff appropriately for OutsourcingStaff appropriately for Outsourcing Thank you! Questions? Paul Woitach, Pharmaceutical Advisors, LLC


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