Download Building, Managing and Continuously Improving Clinical

IQPC Clinical Trial Supply Europe, Basel, February 1 2012
Presented by:
Hedley Rees, Director
AGENDA
 Where are we now in the Pharma supply chain?
 What could the future hold?
 Case study: Perfect Pills and Potions
 Discussion
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The Supply Chain Fragments….
 1970's:
 Prevailing business model vertical integration
 local market management presence.
 predominately small molecule manufactured by chemical synthesis.
 1980’s
 Outsource non-core activities
 Manufacture, analytics, distribution, storage
 Since
 New business models - innovator, virtual, biotech, generic/bio-similars and speciality
Pharma
 Biologics form important portfolio position, with temperature and time sensitivities
 Markets have globalised into new territories
 Number and location of third party contractors and service providers proliferate.
A typical Pharma supply chain
Current state supply-chain
Starting
Material A
Supplier 1
CTS Labels
Supplier 12
Starting
Material A
Supplier 2
CTS &
Storage
Supplier 11
Regional
Depots
Starting
Material A
Supplier 3
API
Supplier 4
Tablets
Supplier 8
CTS &
Storage
Supplier 10
Investigator
Sites
Starting
Material B
Supplier 4
API
Supplier 5
Tablets
Supplier 7
Finished
Packs
Supplier 9
Marketing
Partners
Bottles
Supplier 14
Packaging
Supplier 13
Starting
Material B
Supplier 5
Starting
Material B
Supplier 6
Generic Supply-Chain
- Material Flow -
In-Place
Planned
Information, information, information….
Material disposition status
Analytical
Chem Ops
Oversee process
development.
Contract Ops Manuals
(COM)
Master Batch Record
review.
Master Validation
Protocols
Batch record review
Material disposition
Shelf life determination
Batch
record
CofA
MBR
creation
& approval
Supply Chain
Methods development
Methods Transfer
Review of test results
QA
Monthly
rolling
forecasts
Batch
record
Pharm Ops
Oversee process
development.
Contract Ops Manuals
(COM)
Master Batch Record
review.
MPS model.
Boundary scenarios
Supply agreements
Risk Assessments.
MBR creation
& approval
Batch record
Batch record
Territory.
Market responsibility (CoProm?).
Annual rolling fcorecast.
PO’s
Anti-counterfeiting.
Trade dress definition.
Purchase
order
Invoices
Inventory
report
Manufacturing schedule
Request to ship
Partner
Schedules
for review
Request
to ship
MBR
creation
& approval
MBR
creation
& approval
Inventory report
Updated monthly
schedule (per
supply agreement)
CofA
Print ready
artwork
Starting
Materials
CofA
Buy to spec.
commercially available
Identity check
Release testing
CofA’s
API
CofA
CofA
Shelf life starting point.
Hold time(s)
Stability data
Shelf life/re-test
I
Drug Product
I
Packaged
Product
Distribution
Centre
Registered shelf life
Need to store buffer
inventory for partner
(x months)?
Store product to GMP
I
I
I
Artwork Origination Contact UK
Schedules
Secure GMP
Store
Packaging
Printers - US
Hold starting materials &
API
Real time inventory
Transfer order from
Supply Chain
Need material specs
Samples required
Flexibility to deal with
changes
Concept
artwork
Make print-ready artwork
GNE/OSI approval
Compatible with
packaging contractor
needs
Samples
Artwork
Supply chain foundations begin in drug
development
How the supply chain is formed
Sponsor
Company
Supplying Pre-Clinical Programs
Sponsor
Company
Typical End-to-End Supply Chain – First in
Humans Study
•Initial dosage form may be compromise eg hard gel
capsule.
•Can disguise issues such as poor dissolution
profile.
•Final dosage form may be compromise.
•Initial inertia to change established.
•Filing contains sub-optimal data.
•Sourcing options limited by filing.
•Locked-in to processes, contractors and other
Value Chain parameters.
Examples of potential issues
Sponsor
Company
•Initial dosage form may be compromise eg hard gel
capsule.
•Can disguise issues such as poor dissolution profile.
•Final dosage form may be compromise.
•Initial inertia to change established.
•Filing contains sub-optimal data.
•Sourcing options limited by filing.
•Locked-in to processes, contractors and other Value
Chain parameters.
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Examples of potential issues
Sponsor
Company
Cost
Material price
Yield losses
Batch failures
Re-work
Age-expiry
Quality
100%
inspection
Investigations
CAPA
Customer
complaints
Delivery
Performance
Long lead times
Stock-outs
Shortages
Customer returns
The 21st Century Initiative
 Pharmaceutical cGMP’s for the 21st Century – A Risk-
Based Approach:
 Started 2002 and reported late 2004
 Desired state:
“A maximally efficient, agile, flexible pharmaceutical
manufacturing sector without extensive regulatory
oversight.”
Dr. Janet Woodcock, the U.S. Food and Drug Administration's Deputy
Commissioner for Operations
History of improvement in production
systems
 Industrial Engineering (IE)
 Total Quality Management (TQM)
 World Class Manufacturing (WCM)
 Theory of Constraints (ToC)
 Toyota Production System (TPS)
 Systems Thinking
 Deming wrote the book over 50 years ago!
The Supply Chain Holistic
 Production & Inventory Control (P&IC)
 Procurement
 Transportation, storage and delivery
 Information Systems/Information Technology (IS/IT)
 Improvement
 Integration
Linking up the value chains
Lean background
 NUMMI study, Womack & Jones “The Machine That




Changed the World”
Based on Toyota Production System (TPS)
Reduce time between getting order and money in
 Respect for people
 Continuous improvement
Five principles
Many parallels with TQM, WCM, TOC, etc.
Five Principles of Lean
1. Specify value from the standpoint of the end customer by product
family.
2. Identify all the steps in the value stream for each product family,
eliminating whenever possible those steps that do not create value.
3. Make the value-creating steps occur in tight sequence so that the
product will flow smoothly toward the customer.
4. As flow is introduced, let customers pull value from the next upstream
activity.
5. As value is specified, value streams are identified, wasted steps are
removed, and flow and pull are introduced, continue until a state of
perfection is reached in which value is created with no waste.
Process Village v Value Stream
Traditional functional layout– solid dose
Key points:
Large batches
Produce to forecast
High in-process
inventory
Defects are hidden
Value stream alignment – solid dose
Key points:
Schedule pacemaker only.
Set rate at TAKT (Production rate required to match rate of consumption in the
market place.
Pull from the pacemaker (Kanbans and supermarkets)
Solve production problems (A3 Management)
Take out variation (SPC).
Reduce defect rates on incoming materials.
Use Single Minute Exchange of Dies (SMED) to reduce cycle time
Check list…
 Identifying stakeholders
 Listening to Voice of the Customer (VoC)
 Defining Critical to Quality Attributes (CTQs)
 Creating 'one shared view'
 Analysing the current state map
 Seeing the whole
 Deciding architecture and reach
 Agreeing target and future states
 Developing a control plan
 Gaining organisational buy-in
Questions
If there are any further questions which I was not able to
get to today please feel free to contact me at:
[email protected]