Effectively manage your late phase trials How can CTM deliver the right drugs in a timely and cost e

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Effectively manage your late phase trialsHow can
CTM deliver the right drugs in a timely and cost
effective manner?

• Mike Giffin
• DIA Euromeeting, Vienna
• March 2007

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Since the 80s industries have radically stripped
out costs and speeded up time to market by
streamlining their internal business processes

• Since the 80s other industries have radically
  changed the way they do business
• They have streamlined their supply chain,
  manufacturing and internal business processes
• Modern supply chain management and manufacturing
  optimisation techniques were adopted
• Lean Manufacturing, SMED, 5S
• Blitz Kaizen, Problem Solving
• Sales and Operations Planning
• Just in Time, Kanban, Direct Line Feed
• Visual Workplace, Cellular Manufacturing
• Total Asset Care, TPM
• Applying these techniques has stripped out
  unnecessary costs and capital employed and has
  speeded up total time to market

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Clinical trial supplies have not picked up on
this development, but are now feeling the pressure

• Increased regulations are forcing Clinical
  Development to design Trials that are more
  complex, have longer duration and involve more
  subjects in more locations
• Increased emphasis on ensuring patient safety
• Over the last 20 years, the development time in
  clinical phase has increased by 50
• As a result Clinical Trial Supplies is confronted
  with increased complexity, higher volumes and
  shorter lead times.
• Increased export/import regulations requires more
  knowledge, experience and manpower
• Complex package design increases number of
  packaging materials, resource requirement and
  waste levels
• The time that is allocated to CTS has not
  increased, is even becoming less
• Due to cost pressures, the regulatory
  developments cannot be countered by pro rata
  increase in resources
• Alternatives like outsourcing are an expensive
  source of additional capacity and knowledge

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The lack of proper Clinical Trial Supply Chain
Management jeopardises recruitment and more than
doubles overall clinical trial supply costs

• Overall cost of drug supplies is determined by
  the clinical trial supply chain design
• Traditional forms of packaging are wasteful
  50-75 of drug wastage is not uncommon in the
  industry
• Trial centre kits often contain CTM for a number
  of subjects, causing extensive waste when
  under-recruiting
• Subject packs cover a drug administration period
  of several months, causing waste when a subject
  drops out
• Inflexible manufacturing processes and inaccurate
  forecasts lead to pre-production, high stock
  levels and further drug wastage
• Preproduction of trials causes spikes in workload
  and an imbalance in utilisation of resources
• Inaccurate forecasts lead to wrongful allocation
  of CTM to trial sites and non-availability of
  active drug substance
• Inadequate clinical trial material consumption
  tracking is leading to out of stock situations at
  the trial centres

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• How can CTS deliver the right CTM in a timely and
  cost effective manner?

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It is imperative for CTS to supply CTM based on a
demand pull system

• Flexibility of supplies will have enormous impact
  on how well supply inventories and scrap levels
  can be managed
• A supply chain needs to be established that will
  provide rapid Just in Time turnaround of CTM to
  trial centres
• By applying lean manufacturing concepts, CTS can
  move from a reactive, make to stock push system
  to a demand pull replenishment system
• Actual consumption drives packaging schedule,
  labelling operation and replenishment orders
• Just in Time customisation matches recruitment
• Re-supply of single administration packs based on
  Kanban replenishment principles

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A number of enablers need to be in place before
demand pulling can be implemented successfully
2. Clinical trial supply operations set-up to
provide required flexibility
1. Periodic forum established for collaboration
between trial supply management and trial supply
operations
3. Packaging designed for product pulling,
allowing shipment and storage of the smallest
possible unit
Kanban
Kanban
IVRS pull signal
dispense
Central clinical trial supplies unit
Regionaldistribution centre
Localtrial centres
5. Availability of regional distributioncentres
to ensure high quality, short lead-time supply
of materials
4. IVR system to managetrial centre stocks
andtrigger (re-)supply
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1. Periodic forum established for collaboration
between trial supply management and trial supply
operations

• By applying Sales and Operations Planning
  concepts, a periodic form for collaboration
  between trial supply management and trial supply
  operations in established
• Periodically review forecasts for subject
  recruitments, projected start and finish dates
  and packaging orders
• Tracks actual recruitment rate, orders and
  workload and adjusts plan if required
• Directly links strategic planning and forecasting
  with production planning
• Forum provides early visibility of trial impact
  on resources to take informed asset and manpower
  decisions
• Are critical path tasks sufficiently resourced?
• What options do we have for resources?
• Credible justification for recruitment, training
  needs and outsourcing decisions

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2. Clinical trial supply operations set-up to
provide required flexibility

• Implementing Lean Processes will provide
  flexibility without compromising productivity
• Cellular manufacturing and smooth production
  flows
• Packaging instructions created to support most
  efficient production flow
• Visual Workplace Management
• Intermediate stocks with pull replenishment
  through Kanbans
• Quick set-up of packaging rooms and equipment
• Clear accountabilities aligned with a balanced
  set of performance measures
• Use a light but integrated system that supports
  small batch production
• Electronic creation and tracking of (master)
  batch records
• Inventory management
• Batch allocation and materials reconciliation
• Creation of shipping documentation with country
  knowledge base
• Order/shipment tracking

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3. Packaging designed for product pulling,
allowing shipment and storage of smallest
possible unit

• Trigger shipment to the trial site through the
  actual recruitment or clinical trial material
  consumption rate (Kanban pull signal)
• To enable this, design the packaging for product
  pooling
• Dispense small units to the subject, rather then
  a complete subject kit for the duration of the
  trial
• Each kit is uniquely numbered, but not linked to
  a specific randomization block
• This way It is possible to dispense any unit
  within the same randomization category to the
  patient, reducing total waste
• Design the supply chain to minimize lead-times
  for (re-)supply
• Small batch sizes
• Kanban controlled Work In Process stocks
• Multilingual labels/booklets allow supplies to be
  distributed to all or most clinical sites
  involved in the study

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4. IVR system to manage trial centre stocks and
trigger (re)-supply

• Main benefit of an IVR system is in overall
  clinical trial management
• Improves data accuracy and availability
• Improves subject diary compliance
• Reduces effort in data management
• However an IVR System also balances the inventory
  at the trial sites, minimising wastage of drugs
  due to excessive stocks, without jeopardising the
  availability of CTM
• IVRS Improves clinical supplies forecasting and
  povides clinical trial material consumption
  tracking
• IVRS provides the Kanban trigger for (re-)supply
• Automatically selects correct subject kit and
  manages randomisation, allowing smaller trial
  centre kits
• Improves inventory and expiry date management at
  the trial sites

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5. Availability of regional distribution centres
to ensure high quality, short lead-time supply of
materials

• The use of regional distribution centres plays an
  important roll in reduction of (re-)supply
  lead-times to the trial centres
• Decision on quantity and location of regional
  distribution centres depends on
• Clinical trial intelligence to determine the
  regions where clinical trials will be conducted
• Required lead-time
• What is the potential savings due to less scrap
  at the trial centre
• Expected operational costs (resources, building,
  equipment, information system, transport)
• Regulatory issues, import licences, local
  legislation
• How long it takes to receive customs clearance
• Outsourcing or in-house

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Implementing lean concepts will ensure you can
effectively manage your late phase trials,
reducing total cost of supply by more than 40

• Flexibility in the supply chain will be
  established by implementing Kanban and JIT
  principles, moving from a CRF push to a demand
  pull system
• Increased flexibility will guarantee on time
  availability of CTM to meet the recruitment at
  the trial centres
• Overall drug wastage will be more than halved,
  freeing up drug substance and budget for clinical
  development
• Demand management and capacity planning will
  smooth workload and provide early visibility of
  trial impact on resources to take informed asset,
  manpower and outsourcing decisions