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Technology Transfers & Quality
Kenan Kösoğlu
Novartis Ürünleri
Eskişehir, 25th May., 2012
Technology Transfer & Quality
Quality
 Quality not only concerned with the drug product
What is QC ?
 Quality also needs to be considered & comprehend all activities around
the production / tech transfers
What is QA ?
 Documentation
 Communication
 Project management
 Change management
 Rules & Regulations (GMP, corporate, Health Authorities, legal requirements, etc...)
 Production process
 Quality control process, standard operation procedures, manuals
 All other activities related production process
 We need to assure fast “time to market “ and continuous supply with Quality at competitive
cost while leading tech transfers with minimized one time cost.
2 | Tech Transfer & Quality / Novartis / May.2012
Technology Transfer & Quality
Objectives & Reasons of Technology Transfers
 Technology Transfer
 from R&D to regular (large-scale) production
 from site to site (regular productions)
why tech transfers needed?
 Objectives / Reasons :
 Strategy of production site / corporation
• Capacity optimization & harmonization
• Technology of Granulation, Tabletting, Coating
• Site area changes
• Productivity & financial effectiveness of the site/company
• Life cycle of the products & site product portfolio management
• Dosage forms (TAB, FCT, SCT, Capsules, EFT, LOZ, ...)
 Pharmaceutical Sector
• Legal requirements of products, production process & regulations
• Product base changes & competition
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Technology Transfer & Quality
Life Cycle of products
Good LCM means optimising lifetime brand performance, every
time, within the context of the overall product and project portfolio
Sales
Development
Growth
Maintenance
Decline
Orphan indications
Phase IIIB / IV
New indication/ new dose in new formulation
New indications
IITs
Pediatric formulation
Local LCM
FDCs
New indications
Drug delivery
Milk
Sec. patents
FDCs
New salt
New formulations
Sec. patents
OTC switch
New doses
New formulations
Defend patents
Pediatric formulation
Re-purposing
New doses
Foster
Divest
Prune
Successor molecules (research or BD&L)
New dosage regimens
Raise purity / BEQ standards
Regulatory exclusivities
Packaging innovation
Data protection
Lean manufacturing
New chemistry
New processes
Loyalty programmes
Volume purchasing contracts
Publication strategy
Geographical expansion
White papers
Authorised generics
Time
When to start for Tech Transfer Projects ?
4 | Tech Transfer & Quality / Novartis / May.2012
Focus on self-pay markets
Technology Transfer & Quality
Project Management Tool in Technology Transfers
 Scope
 Complexity of the project
 Local vs. multi market , # of SKU, # of countries, dosages, etc
 Cost :
 Project budget, cash flow, investment management
 Time management :
 Launch the products within planned time
 Resource Management :
 Human, Technical Know-how, Machine & Equipment
 Stakeholder management
 Project sponsor, manager & team with roles & responsibilities
Who will be in project team ?
5 | Tech Transfer & Quality / Novartis / May.2012
Technology Transfer & Quality
Environment
 We are living in global environment which effect directly decisions
and plans on tech transfers. Requirements need to be followed and
applied properly during tech transfer projects :
 Patients
 Doctors, universities, ...
 Diseases
 Health Authorities (all countries) , government & legal requirements
 Corporate requirements
 Pharmaceutical Sector & GMP Rules
 World technology trends
Samples of environment effects on tech transfers?
6 | Tech Transfer & Quality / Novartis / May.2012
Technology Transfer & Quality
Functions in Organization during the Transfer
 Quality do not focus only the production . It is must that all activities
within the organization (cross-functional) needs to be managed
considering Quality.
 Project management
 Health, Safety & Environment
 Supply chain management / logistics
 Regulatory & Medical
 Marketing
 Engineering
 Quality Assurance & Quality Control
 IT Systems
 Legal requirements
• Finance
Why Quality needed for those activities too ?
• Personal
7 | Tech Transfer & Quality / Novartis / May.2012
Technology Transfer & Quality
Phases in Tech Transfer
 Evaluation & Approval Phase
 Financial & Technical Ffeasibility of the tech transfer, capability & resource mang.
 Planning Phase :
 Tech Transfer Project plan : Who, What, When, How,..
 Technical Phase :
How much time needed for each phase ?
 Validation productions as per Planning Phase
 Regulatory & Registration Phase :
 Regulatory documentation & submissions to Health Authorities
 Logistics & Execution Phase :
 To ensure the first supplies properly as per planned at the previous phases
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Technology Transfer & Quality
Evaluation & Approval Phase
 Corporate & Site strategy
 Current & long term site capacity
 Investment need, tooling , equipment (technical feasibility)
 Incremental human resources need
 Available technology, infrastructure, layout , know-how
 New countries, audit requests
Which risks available & how to
 Product basis requirements
eliminate them?
 Project volume figures
 Brand life cycle status & long term forecasts
 Competition & generics
 Regulatory requirements by Health Authorities
 Financial figures & costs (financial feasibility)
 Cost per pack
 Cost per worker
9 | Tech Transfer & Quality / Novartis / May.2012
Technology Transfer & Quality
Planning Phase (Transfer Master Plan-1)
 Validation Strategy
 Process Validation Protocol
Why planning phase is most cruical ?
 Packaging Validation Protocol
 Cleaning Validation studies
 On-site technical visit & good communication practice between GS vs. RS
 Qualification, calibration & comparison of equipments, infrastructure
 Product annual review data , previous trends (stability, OOS, etc..)
 Update, review current process before the tech transfer, check lessons
learned from previous tech transfers, review GS documentation & knowledge
 Site production area conditions (temperature, humidity, light, ..)
 Evaluate all IPC (test methods & specifications) & plan all parameters
 Planning of manufacturing lines, equipment & infrastructure :
• Decide which lines will be used for the related tech transfer
 Check microorganism requirements
 Prepare master batch records/production documents before the validation production.
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Technology Transfer & Quality
Planning Phase (Transfer Master Plan-2)
Importance of Stability studies ?
 Registration Strategy
Importance of Dissolution profile test studies ?
 Stability Protocol, conditions, shelf life decision
 Method Transfer (lab to lab) : Lab capacity & capability
 TM Testing Monograph update if needed (raw mat., drug product,..)
 Dissolution profile requirements (medias, conditions, time points, ..)
 Raw Material & Drug substance specs, comparison & supplies
 Pack material specs, comparison & supplies
 Change management (trace & document all changes)
 Document transfer , know-how & information from R&D & giving sites
 Plan GMP audits / inspections in case needed
 Country approvals ( 1-24 months)
 Submission strategy & groupings
• EU Countries with 3 months stability data
• RoW Rest of the World countries with 6 month stability data
 Evaluate Health Authority requirements during planning phase and take
into consideration properly not to face conflict at registration phase
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Technology Transfer & Quality
Planning Phase (Transfer Master Plan-3)
Importance of planning logistics strategy at
 Logistics Strategy
planning phase ?
 HSE requirements of the transferred product
• Transport conditions, storage conditions
• Product status (hazardous, flammable, ..)
 Technical requirements of pack materials and availability
 Data management, system definitions
 Transfer check list
 Site Storage & warehouse conditions (temperature, humidity, light, ..)
 Train all staff concern with the transferred product & process
 Get ready in terms of purchasing, supply chain, logistics
 If needed perform investment plans
 Bridging inventory calculations
 Plan the budget & resource management
 Plan communication management tools
• Regular informative & decision meetings
• Committee meetings, status reports
12 | Tech Transfer & Quality / Novartis / May.2012
Technology Transfer & Quality
Technical Phase
 Perform the validations as per
Which difficulties could be in technical
 Transfer Master Plan
phase ?
and
 Documents & information decided at Planning Phase
 Validation Report
 Stability tests & studies
 Stability report
 Perform dissolution profile comparison tests within both sites
 Dissolution profile comparison report
 Executed Batch Records / production
 QC release & test results
 All changes & deviations needs to be classified & documented (planned
protocols vs. actual reports)
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Technology Transfer & Quality
Regulatory & Registration Phase
 Collection of the documentation created from technical phase
 CMC document writing
 Communication with all stakeholders to perform the documentation
properly considering Quality.
 Submissions to Health Authorities (HA)
 “right at first time” not to cause variations
 Reply questions from HAs
 Document the changes properly as planned at registration strategy
 Follow approvals & reply HA questions
 Requests from HAs ;
 Samples, Reference materials
 Certificates (GMP, CPP, ...)
 Previous Audit reports
Why “right at first time” is important ?
14 | Tech Transfer & Quality / Novartis / May.2012
Technology Transfer & Quality
Logistics & Execution Phase
 Logistics activities :
 Define production lead-time, minimum order quantities, system
 Definition of the products, raw materials, BOM, Routing, etc...
 Complete the artwork studies as per registered designs
 Start communication & activities with suppliers & customers
 Complete financial activities such as costing & pricing
 Check short, mid & long term plans, capacity
 Last supplies to giving site
 First supplies from receiving sites
 Handover from Transfer Project team to regular functions :
 Correct & on-time handover
How to handover ?
 Full handover might be within 1-3 years
 Alignment of regular productions according to registered process
during the tech transfer
15 | Tech Transfer & Quality / Novartis / May.2012
Technology Transfer & Quality
Best Practices & lessons learned
 Good project planning at Technology Transfers are crucial and this
ensures the volumes at the site as estimated and cause positive effect
on corporate strategy & competitiveness at long term.
Project Planing - Quality
Weak project plans & wrong bridging inventory quantities could cause ;
 Stock-out
 Write-off cost
 One time cost
 Less income
 Risk to loose the brand
 Less reliability of brand / corporation
16 | Tech Transfer & Quality / Novartis / May.2012
Eliminate all risks with
good team working .....
Thank You !
Questions & Answers