Joint CVG/Therapeutic Products Directorate International Convention and Exhibition Toronto, Canada, October 5 - 6, 2006
Technology Transfer Challenges in Pharmaceutical Industry
Le Trong Vu, P. Eng.Manager, ValidationPurdue Pharma
Joint CVG/Therapeutic Products Directorate International Convention and Exhibition, Toronto, Canada, October 5 - 6, 2006
Agenda
Why Technology Transfer
Basic Conceptson How and When
Thoughts on Keys to Success
111
333
222
444
Success Criteria
Joint CVG/Therapeutic Products Directorate International Convention and Exhibition, Toronto, Canada, October 5 - 6, 2006
Why Technology Transfer
The development and transfer of knowledge and technology has
been and will continue to be critical to success in
pharmaceutical industry
Joint CVG/Therapeutic Products Directorate International Convention and Exhibition, Toronto, Canada, October 5 - 6, 2006
Why Technology Transfer
Stages in the Development of a New Medicine
Biological Evaluation
Discovery
4 –10 years
Research Target
Integrated Research
Candidate Drug
Formulation
Patents
3+ years
Commercialization
Launch
Sales
Process Development
Phase I - Clinical Trials
Phase II - Clinical Trials
Phase III - Clinical Trials
3+ years
Exploratory Development
Build/Select API Manufacturing Facilities
Formulation Development
3+ years
Regulatory Development
Manufacturing
Registration
Built/Select Manufacturing
Facilities
Joint CVG/Therapeutic Products Directorate International Convention and Exhibition, Toronto, Canada, October 5 - 6, 2006
Why Technology Transfer
When does technology transfer occur?Idea to Discovery Lab
Discovery Lab to Development Lab
Development Lab to Kilo Lab
Lab to Pilot Plant
Kilo Lab to Pilot Plant
Pilot Plant to Semi-works (other pilot plant)
Pilot Plant/ Semi-works to Manufacturing
Manufacturing to Manufacturing
Joint CVG/Therapeutic Products Directorate International Convention and Exhibition, Toronto, Canada, October 5 - 6, 2006
Why Technology Transfer
Technology Transfer Importance to Industry
Process development and commercial production are on critical path because of compressed time-to-market expectations
Technology Transfer is a vulnerable time for companies
Loss of knowledge or experience, leading to “reinvention of the wheel”Confused ownership and responsibilitiesDelayed approvals
Joint CVG/Therapeutic Products Directorate International Convention and Exhibition, Toronto, Canada, October 5 - 6, 2006
Stakeholders in the Quest for Effective Technology Transfer
IndustryR&DCommercial
Stakeholders
Customers PatientsHealthcare providersThe public
Regulators
Joint CVG/Therapeutic Products Directorate International Convention and Exhibition, Toronto, Canada, October 5 - 6, 2006
Stakeholders in the Quest for Effective Technology Transfer
Regulators’ roles: Protect public health
Standardize regulationsEnsure safe, pure, and effective drug productsDrug approvals
Affect healthcare systemFacilitate and regulate, bringing new, more effective products to market fasterReduce the cost of healthcare
Joint CVG/Therapeutic Products Directorate International Convention and Exhibition, Toronto, Canada, October 5 - 6, 2006
Stakeholders in the Quest for Effective Technology Transfer
Industry’s role: Innovative R&D
Develop new, more effective compounds, delivery systems, and medical devices
Compliant and effective commercializationEnsure safe, pure, and effective drug productsConsistent interpretation of GMP regulationsBringing new, more effective products to market faster Adherence to all applicable regulations and guidelinesCost-effective production and distributionSuperior return on investment to shareholders / stakeholders
Joint CVG/Therapeutic Products Directorate International Convention and Exhibition, Toronto, Canada, October 5 - 6, 2006
Stakeholders in the Quest for Effective Technology Transfer
Customers & Patients:Safe and effective treatments
New, more effective products to market faster
Affordable healthcare cost
Election of governments
Joint CVG/Therapeutic Products Directorate International Convention and Exhibition, Toronto, Canada, October 5 - 6, 2006
Technology Transfer – A Paradigm Shift
Continuous Knowledge Transfer Industry’s Paradigm Shift
Continuous transfer of knowledge and technology
Improved “lifecycle” management
Good business practice
Speed to market
Globalization
Advances the state-of-the-artProject Conception Launch
Invo
lvem
ent
Research and DevelopmentCommercial Operations
Joint CVG/Therapeutic Products Directorate International Convention and Exhibition, Toronto, Canada, October 5 - 6, 2006
Technology Transfer – A Paradigm Shift
Research and Development Commercial Operations
Project Conception
Launch
Invo
lvem
ent
Regulatory Stakeholder Opportunities
Highly interpretable regulations and
guidelines
Intermittent transfer of knowledge
Reactive inspection and review practices
Reg
s &
Gui
delin
es
Pre-
IND
IND
Pre
Continuous Knowledge Transfer
-Tri a
l sse
s II
&
A t prov
al
Pha
III
ND
PAI
Pos
Ap
Project Conception
Invo
lvem
ent
Joint CVG/Therapeutic Products Directorate International Convention and Exhibition, Toronto, Canada, October 5 - 6, 2006
Technology Transfer - How and When
Knowledge Transfer Process
Need an effective transfer process that plugs the leaks and yields better retention
Joint CVG/Therapeutic Products Directorate International Convention and Exhibition, Toronto, Canada, October 5 - 6, 2006
Then a miracle occurs…
“I think you need a few more details here in the Transfer protocol”
R&D Processes…
Commercial Operations …
Joint CVG/Therapeutic Products Directorate International Convention and Exhibition, Toronto, Canada, October 5 - 6, 2006
Technology Transfer - How and When
ISPE Guide for Technology Transfer
Joint CVG/Therapeutic Products Directorate International Convention and Exhibition, Toronto, Canada, October 5 - 6, 2006
Technology Transfer - How and When
TT Guide is designed to:Present standardized process
Recommend minimal base of documentation to support the technical transfer process
Define key terms and consistent interpretation
Facilitate timely and cost effective technology transfers
Consider regional requirements of US, Europe and Asia (Japanese Ministry of Health Labor and Welfare)
Joint CVG/Therapeutic Products Directorate International Convention and Exhibition, Toronto, Canada, October 5 - 6, 2006
Technology Transfer - How and When
TT Guide & Manufacturing Science
Encompasses Research, Development, Analytical, Process and Quality
Guide focuses on the level, quality, and type of Information
Enables the capture and sharing of the “Right Knowledge”
Joint CVG/Therapeutic Products Directorate International Convention and Exhibition, Toronto, Canada, October 5 - 6, 2006
Technology Transfer - How and When
Technology Transfer Task Relationships Model
Joint CVG/Therapeutic Products Directorate International Convention and Exhibition, Toronto, Canada, October 5 - 6, 2006
Technology Transfer Success Criteria
Success Criteria?
"You can tell pharmacy we finally have three batches of on-spec product."
Joint CVG/Therapeutic Products Directorate International Convention and Exhibition, Toronto, Canada, October 5 - 6, 2006
Technology Transfer Success Criteria
What Constitutes A Successful Technology Transfer?*
Success criteria from Definition of Technology Transfer:“… ability of a Receiving Unit to … perform …transferred technology, to the satisfaction of all parties and any, or all,
applicable regulatory bodies”
“Technology transfer can be considered successful if a Receiving Unit can routinely reproduce the transferred product, process or method against a predefined set of specifications as agreed with a Sending Unit and/or a
Development Unit.”
*From ISPE Technology Transfer Guide
Joint CVG/Therapeutic Products Directorate International Convention and Exhibition, Toronto, Canada, October 5 - 6, 2006
Technology Transfer Success Criteria
Success Criteria: Demonstrate with data conformance to success criteria standards as outlined in the technology transfer plan:
Process parameters and control mechanisms
Material suppliers
Analytical methods
Health, safety and environmental concerns
Compliance with all registered commitments
Joint CVG/Therapeutic Products Directorate International Convention and Exhibition, Toronto, Canada, October 5 - 6, 2006
Technology Transfer Success Criteria
Technology Transfer must also be completed:
Safely
The process being transferred runs as expected (yield, purity, cycle time, etc.)
On time (product launch)
On budget
No “CRISIS” situations
There Is More To Successful Technology Transfer:
Joint CVG/Therapeutic Products Directorate International Convention and Exhibition, Toronto, Canada, October 5 - 6, 2006
Technology Transfer Success Criteria
Change Control
Audit process performanceStatistical review
Continual process improvement programStatistical process control
Critical Success FactorsPost Approval :
Joint CVG/Therapeutic Products Directorate International Convention and Exhibition, Toronto, Canada, October 5 - 6, 2006
Technology Transfer Success Criteria
If technology transfer isn’t done right…Process validation may be unsuccessful
Delayed regulatory approval and/or product launch
Flawed processing may resultHigh rate of batch rejections, costly schedule revisions, excessive labour requirements
Analytical methods cannot support production
Incomplete documentation
Product does not perform as intended!
Joint CVG/Therapeutic Products Directorate International Convention and Exhibition, Toronto, Canada, October 5 - 6, 2006
Keys to Success
What Is the Key to Successful Knowledge Transfer?
− It Must Be Understood and Managed by ALL Stakeholders
Joint CVG/Therapeutic Products Directorate International Convention and Exhibition, Toronto, Canada, October 5 - 6, 2006
Keys to Success
CommunicationOpen communication between all team members
Direct communication between technical members
Effective and timely communication with regulators
Joint CVG/Therapeutic Products Directorate International Convention and Exhibition, Toronto, Canada, October 5 - 6, 2006
Keys to Success
CommunicationCultural / Organizational Differences
Germany
Austria
Switzerland
Joint CVG/Therapeutic Products Directorate International Convention and Exhibition, Toronto, Canada, October 5 - 6, 2006
Technology Transfer Success Criteria
Sending and Receiving Unit
Technology transfer is not a “one way street”.
The sending unit and receiving unit must be equally involved in the process to ensure success.
FormulationDevelopment
ProcessDevelopment
AnalyticalDevelopment
Production
QualityControl
TechnicalServices
Joint CVG/Therapeutic Products Directorate International Convention and Exhibition, Toronto, Canada, October 5 - 6, 2006
Technology Transfer Success Criteria
Team work, most of the time
Joint CVG/Therapeutic Products Directorate International Convention and Exhibition, Toronto, Canada, October 5 - 6, 2006
Technology Transfer Success Criteria
Effective technology transfer is critical to success in pharmaceutical industry
Commercial
Post Approval
Regulators
APPR
OVA
L
Development
Project Conception
Invo
lvem
ent
Regulators
Regulatory BodiesCommercial OperationsResearch and Development
Joint CVG/Therapeutic Products Directorate International Convention and Exhibition, Toronto, Canada, October 5 - 6, 2006
Thank You
Joint CVG/Therapeutic Products Directorate International Convention and Exhibition, Toronto, Canada, October 5 - 6, 2006
References
1. ISPE Technology Transfer Guide, 2003
2. F. Sexton, Effective and Efficient Knowledge Transfer from R&D to Manufacturing, Purdue Pharma’s SMC Meeting, March 2004
3. G. Millili, Ph. D, Technology Transfer: Manufacturing Perspective, Pharm Tech Conference 1996
4. S. Liebowitz, Ph. D, Pharmaceutical Technology Transfer: Pre and Post NDA Submission, Pharm Tech Conference 1995