1. Technology Transfers & Quality Kenan Kösoğlu Novartis Ürünleri Eskişehir, 25th May., 2012

2. Technology Transfer & 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.
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3. 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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4. Technology Transfer & Quality
Life Cycle of products
When to start for Tech Transfer Projects ?
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5. 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 ?
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6. 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?
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7. 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
Personal
Why Quality needed for those activities too ?
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8. 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 :
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
How much time needed for each phase ?
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9. 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
Product basis requirements
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
Which risks available & how to eliminate them?
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10. Technology Transfer & Quality
Planning Phase (Transfer Master Plan-1)
Validation Strategy
Process Validation Protocol
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.
Why planning phase is most cruical ?
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11. Technology Transfer & Quality
Planning Phase (Transfer Master Plan-2)
Registration Strategy
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
Importance of Stability studies ?
Importance of Dissolution profile test studies ?
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12. Technology Transfer & Quality
Planning Phase (Transfer Master Plan-3)
Logistics Strategy
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
Importance of planning logistics strategy at planning phase ?
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13. Technology Transfer & Quality
Technical Phase
Perform the validations as per
Transfer Master Plan
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)
Which difficulties could be in technical phase ?
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14. 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 ?
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15. 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
Full handover might be within 1-3 years
Alignment of regular productions according to registered process
during the tech transfer
How to handover ?
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16. 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.
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
Project Planing - Quality
Eliminate all risks with good team working .....
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17. Thank You !
Questions & Answers