Packaging of Clinical Supplies Logistics and Practical Aspects of Packaging

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Packaging of Clinical SuppliesLogistics and
Practical Aspects of Packaging Labeling CTMs

• Michael S. McNear R.Ph.
• Fisher Clinical Services
• Allentown, PA

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Outline

• PlanningPlanningPlanning
• Labeling Concepts
• Packaging Concepts
• Summary

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Where It All Starts

• Clinical Trial Material Professionals must be
  involved in the protocol planning and conception
  stages
• This does not mean medical fills out a form and
  sends it to you.
• It involves active participation in all aspects
  of the study planning process from the earliest
  possible time point.

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Basic Facts

• Bulk chemical or drug supply availability and
  timelines
• Dosage forms available
• Protocol scope (where?)
• Available stability information
• Study Start Date

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Study Start Date

• Is it negotiable?
• Initially no..
• As time goes on..maybe
• Clinical Supply Professionals must be informed
  and involved. Study initiation is complicated
  for all aspects of the process and the start date
  is likely to move.how effective is your CSM
  organization at knowing the real date??

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Early Decisions Program Level

• Comparator choice/strength and blinding
  considerations
• Need for new analytical methods
• Need for new stability data
• Start multiple programs.what is not needed can
  always be cancelled
• Visit Schedule(s)
• Critical to package concept design

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Early Decisions

• Proposed dosing information
• Any manufacturing/packaging considerations
• Humidity control
• Light Sensitivity
• Logistics
• Temperature control
• Hazardous transport

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Early Risk Assessment

• Failure to begin research about the comparator,
  blinding, analytical and stability information at
  the protocol inception phase is one of the
  greatest risks to study delay.
• Research multiple comparators
• Risk is minimalbuild in milestones for actual
  large expenditures

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Early Risk Assessment

• Logistics - Especially the participating country
  list.
• Language consideration
• Import/export considerations
• EU release issues
• Comparator sourcing
• Transport considerations
• Start with a list of all possible countries with
  a commitment to update regularly

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Moving Forward Considerations and decisions
that must be made BEFORE protocol finalization

• To IVR or not IVR
• IVR can be an effective tool for nearly any study
• Keep it simple
• Detailed specifications with Medical
• Standardization concepts work!

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Moving Forward

• Global Kits with multi-lingual labeling
• For all multi-national trials, always seems like
  a good solution
• Can you effectively decide countries soon enough?
• Do you have an effective translation regulatory
  approval process?
• One country can delay the world
• Consider Phased approach

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Moving Forward

• Package Design
• Study concept driven
• Bottles vs Blisters
• Need to keep patient compliance as the primary
  driver
• Kit Flexibility
• Can one kit type be used for the entire study?
• Directly affects IVR design and functionality
• Can any of your organizations standardization
  concepts fit the study needs??

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Moving Forward

• Logistics
• Definitive plan for assessing the supply chain
  logistics
• Depot considerations
• Direct to site vs affiliate involvement
• Temperature control and validation of shippers
• EU regulations
• Carrier/delivery level considerations

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Continuing Risk Assessment

• As protocol continues development, risk/reward
  assessments with your clinical partner must
  continue.
• Countries Labels, regulations, regulatory
• IVR
• Comparator
• Stability
• Package Design Perhaps even some primary
  packaging activities
• Logistics

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Onward!!

• Operational execution/excellence
• No matter the level of expertise, capacity and
  operational savvy, 16 weeks of work can not be
  done in 4 weeks.or can it??
• Parallel vs sequential activity planning
• Requires communication among operational
  functions involved
• Low level risks
• Manufacturing and packaging at risk

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Onward!!

• Leverage internal expertise and strengths
• Consider contractor involvement
• Capacity
• Expertise outside of core competency
• Engineering solutions
• IS/IT solutions
• Key factor is earliest possible decision to
  outsource (I.e the planning stage)

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Onward!!

• Partial vs complete study supply preparation
• Realistic view of how fast study might enroll
• Might one region of the world come on several
  weeks before another?
• IVR designflexibility of kits to be used for any
  patient/visit combination

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Onward!!

• Communication Things will change..does your
  relationship, organization strive for constant
  feedback about study start timelines or other
  critical study parameter changes??
• Continual timeline adjustments
• Hallway chats!! Are you visible?

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How??

• Spending the time and resources to be involved
  from day 1
• Providing a service and expertise focused on
  solutions.not how hard/complicated my job
  is.Providing the Yes if..answer
• Gaining trust and respect from your Clinical
  colleagues

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How??

• Shared Risk assessment and actions
• Defined formal and informal communication
  channels
• Creative solutions
• Hitting your Hot Spot
• Ethical, professional behavior

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How??

• Dedication to Planning Too many times we claim
  that this business can not be plannedI think
  quite the opposite. Plan with gusto the bits and
  pieces that can be planned.dedicate yourself to
  it.it will eventually allow you more time and
  energy to deal with the events that truly can not
  be planned or controlled..and they will happen!!

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Labeling Concepts

• Practical Considerations
• Style
• Multi-Lingual Labeling
• Just-In-Time (JIT) Concepts
• Exp. Dates and the EU

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Practical Considerations

• 1 Ensure focus remains getting the correct
  label on the correct container.not theres a
  broken letter in the caution statement.
• Ensure Identifying number usage instructions
  are the most visible (size).
• Ensure Exp./retest date information is in a place
  where it can be easily updated.

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Practical Considerations

• Label text has two main purposes.
• Does it give the patient/subject the best chance
  of understanding how to correctly take the
  medication
• Does it give the site dispensing the medication
  the best opportunity to give the correct
  medications to the patients/subjects
• FOCUS on these

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Style

• One paneltwo panelthree panelbooklet
• No IVRS Two or three panel is appropriate on
  the dispensing unitall others should be one
  panel.
• IVRS Leverage the system capabilities/control
  and consider one panel labels for ease of
  application AND site efficiency.

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Style - Booklet Labels

• All the Rage!! Excellent choice for
  multi-lingual presentations..but
• Will one country in the world be rate limiting to
  study initiation?
• How efficient is your translation/regulatory
  approval process?
• Consider practical country groups as a strategy

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Multi-Lingual Labeling

• 1 concept employed in global trials today.
• Booklets
• Standard labels
• Blister cards
• Boxes and cartons

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Exp. Dates and the EU

• New regulations in the EU clearly state that if
  dates are controlled by electronic (IVRS) like
  systems that Exp. Dates DO NOT need to be on the
  container (similar to the US regulations)
• Time will tell the application of this in trials,
  but we should challenge and support this.
• Some trials HAVE been done with this principal.

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JIT Labeling

• Concept that all or some of the labeling is added
  just in time.typically at the time of
  distribution.
• Most commonly used for Exp./retest dates
• Can be a powerful tool
• In my opinion, must be controlled electronically
  i.e. barcodes or vision systems

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Multi-Lingual Labeling

• Practical Considerations
• Off-set print as much as practical
• Even more critical to keep in mind general
  labeling considerations like unit identifier and
  instruction clarity/size
• Critical to use universal symbols like the moon
  and sun
• Challenges as discussed with booklets.
• Do not let the label challenge FPV!

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Packaging Concepts

• Package Types and Stability
• Blinding Considerations
• Standardization Concepts
• Start At The End
• Automation
• Total Control

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Package Types

• Package type and style should have only one
  guiding principal
• Patient Compliancenever compromise
• When packaging for IVR studies consider packaging
  to the lowest common denominatorincreases
  flexibility
• Consider the site storage situation

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Package Types

• Consider the dosing regimen and the possible
  affect that may have on the card size/style.if a
  dose is needed at mid-day, the card should be
  able to be carried with the patient easily
• Consider ease of machine set up and flexibility
  of short run operations in material/component
  choices

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Stability

• Dont wait until the protocol is finalized.
• Utilize standard materials/components
• Apply bracketing principals
• Consider comparators at the program level and get
  them on stabilitythey can always be stopped
• Perfect low riskhigh reward scenario

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Blinding Considerations

• Most common way to un-blind site personnel is
  with packaging issues
• Label placement differences
• Different color shades
• Multiple component lots
• Regular use of multi-room/shift packaging
  strategies

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Blinding Considerations

• Use strict control of packaging components to
  avoid small visual differences
• Use as many visual aids as possible
• 3-D drawings
• Digital pictures
• Samples
• Dont forget tamper seal placement as well!!

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Standardization Concepts

• They work!
• Film and foil
• Bottling components
• Standard card types
• Standard terminology
• Label stock/style
• Can sometimes borrow stock components from the
  commercial side of the businessBUT
• Proceed with caution

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Start at the End

• Today the logistics involved with global CTM
  materials can be as or perhaps even more complex
  than the packaging. Consider the warehousing,
  distribution and handling of the goods at the
  planning stages.

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Start at the End

• Consider.
• Single layer pack outsespecially for IVRS type
  studies
• Identifying any pre-pack activities that can
  happen prior to distribution
• IVRSSequential vs. Random kit identifiers
• Random may be better, but pack out and IVR
  coordination are critical. Safer if used with
  electronic checking means as well

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Automation

• Look for every opportunity to automate any part
  of the process possible
• Best for large long term trials or entire
  programs
• Need for early planning with engineering
• Validation and testing
• May require specific IS controls and systems
• More validation and testing!

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Total Control

• Concept of utilizing barcodes to
• Verify and count labels in printing operation
• Control and verify packaging processes
• Verify correct item is shipped to site
• Record product returns for reconciliation purposes