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The Clinical Trial Supply Chain – Before and After the Trial Start

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					    The Clinical Trial Supply Chain – Before and After the Trial Start
                                  Date

Everybody is more than familiar with          •   Appropriate storage of completed
the fact that clinical trials generally are       and released supplies
getting larger, more complex and              •   Packaging and labeling of supplies
reaching to the farther edges of the          •   Material requirements for
globe. Not to mention that the                    packaging and labeling
timeframes involved are shrinking! In         •   Production and supply of bulk IMP
the world of outsourcing, a lot of trials
seem to come as a surprise, both to the       Acting on this information alone,
client and to the vendor, with whom           shared in soft focus with either an in-
they partner in the packaging and             house clinical supply unit or potential
distribution process. Each party has a        vendors allows a certain amount of
distinct common goal in terms of              pre-planning. This in itself can start to
reaching the effective trial start date       reveal potential problems, bottlenecks
(first patient in) and ensuring that each     and possibly some solutions for: -
patient and site is supplied with the
correct medication at the right time.         •   Bulk drug availability
                                              •   Material purchase lead times
Clinical trial supplies more often than
                                              •   Production capacity constraints
not occupy the critical path bottleneck
                                              •   Opportunities to produce generic
in terms of availability, therefore
                                                  stock that cross several trials
affecting cycle times for getting new
drugs to market. There are a number of
best practices and tools that can be
                                              Often, it is seen that in effect the actual
used both before and during the trial to
                                              required start date for trial activities
ensure that the clinical supply chain is
                                              has already passed. It is useful, when
managed more effectively and operates
                                              preparing the Protocol for the clinical
more efficiently.
                                              trial, that the Clinical teams plan a time
                                              point when individual clinical supply
Working backwards
                                              requirements are “frozen”. This allows
                                              the ticking clock for trial start date to
Sponsor companies should have a plan
                                              be reset after any alterations to the set
of activities; this should not be a
                                              supply requirements. Examples for this
crystal ball exercise. Lead candidates
                                              are primary packaging, kit formats,
and pipelines for each year generally
                                              required quantities and everyone’s best
are known in advance (1-2 years) and
                                              friend, label text.
this information can be a precursor to
                                              The clinical supply chain must be seen
demand forecasting and production
                                              as a global one – from raw materials
planning if shared and used correctly.
                                              right through to world-wide
The clinical trial start dates work
                                              distribution to customers (the patient).
backwards for both the sponsor, and
outsourcing partner in terms of being
able to identify the lead times for :-

•    Shipping to the study sites (after all
     necessary approvals are in place)
                The Clinical Trial Supply Chain – Before and After the Trial Start
                                              Date

                                                                       the initial supply of kits become
                 Clinical Supply Inventory Chain
                                                                       absolutely critical to continuous patient
BULK IMP
                                                                       supply. Now we enter a crucial phase.
                                                     Site inventory
                              CENTRAL
Packaging
components
                              PACKAGED                                 After study initiation, monitoring of
                              TRIAL SUPPLY
                              STOCK
                                                                       clinical supply inventory throughout
                                                     Depot inventory   the supply chain is essential in order
Label text
                                                                       to: -

             Trial FPI date              Resupply – trial running      •   Examine study kit usage and
                                                                           available stock levels
                                                                       •   Ensure the drug is always available
              Figure 1- Working back from expected                         for patients
              First Patient In (FPI) Date                              •   Minimise waste medication (it is
                                                                           expensive!)
                                                                       •   Alert sites in case of potential
              When there is an overview of all                             supply delays
              scheduled trial supply requirements,                     •   Comply with GMP/ GCP
              the planning process can enter into a                        conditions such as expiry date
              more detailed phase noting each                              management and accountability
              deliverable component required to
              produce the supplies for the study start
              date. Without going into the mechanics
              of project management, the trial
              manager will of course balance CTA                       Approaches to clinical trial supply
              submissions and approvals, along with                    management
              country specific requirements, in
              parallel with the production of the                      Once a trial starts and recruitment gets
              clinical trial supplies and its associated               into gear, supply stock levels often
              inventory chain.                                         start to deplete at a different rate than
                                                                       expected. Add to this the needs of
              Stock levels and tracking of clinical                    expiry date management and soon
              trial supplies                                           supplies can start to dwindle. It is
                                                                       essential that stock level data is
              Once the clinical trial supplies are                     monitored throughout the entire supply
              available to commence a trial, the                       chain, but due to multiple parties and
              tracking and monitoring process can                      systems involved this is not a
              begin to ensure that stock levels of kits                straightforward process.
              are maintained and that the supply to
              each patient is continuous and                           Some large Sponsor companies have
              uninterrupted. Usually for later phase                   inventory and management systems
              trials with large patient populations,                   capable of monitoring various portions
              supplies are delivered in phased                         of the supply chain. However, when
              campaigns, often due to expiry date                      the decision has been made to
              limitations or comparator availability.                  outsource portions of the supply chain,
              This in turn means that stock levels of                  Sponsor companies suddenly find a
 The Clinical Trial Supply Chain – Before and After the Trial Start
                               Date

gaping hole in any materials                 but the Trial Supply Manager must
management systems. Also in most             link the inventory data back into the
instances, once shipped globally,            complete chain. Examples of inventory
supplies can disappear totally from the      management include : -
Sponsor’s radar, therefore creating a
reliance on unconnected reports from
other systems (mostly 3rd party),            The manual approach
which require manual manipulation of
data to forecast future supply needs         Many Sponsor companies employ a
and manufacturing requirements.              manual approach to the supply chain.
                                             Generally this will mean pre-defining
Another inherent problem can be that         set amounts to ship to each site on
various inventory reports and stock          activation and then another set amount
levels are available, but the supply         for further supplies. This can result in
chain is not covered for each required       reduced visibility of the inventory and
component and does not look back in          provide difficulties if sites take on a
totality to bulk material and component      different level of activity than
availability.                                predicted. Supplies are usually
                                             manufactured/ packaged with at least
It is useful to note that as kit inventory   of 100% overage, therefore adding to
is monitored by whatever means               the trial cost and lead times for
selected by the Clinical Managers,           production. Study monitors can
plans must be included to make the           provide inventory verification but this
information available to each                approach can lead to a fragmented
participant in the supply chain. This        approach if multiple supply campaigns
means that outsourcing partners need         are required.
to be involved in relevant data
exchanges that may affect the
availability of additional supplies, and     Use of Interactive Voice Response
that this involvement occurs in a            Systems (IVRS)
timely fashion. In our experience, joint
meetings involving Sponsor companies         Traditionally both IVR, and similar
and associated vendors prior to study        web based systems have been the
commencement are invaluable. Such            scope of large Phase III trials, with
meetings can present a platform to           complex dosing and inventory
examine interface exchanges and              requirements. However the quality of
possible alternative approaches to the       reporting tools available and
study design. Also, it is possible to        management of randomisation has
have one vendor responsible for              encouraged increased use within the
multiple areas of the supply chain,          industry. An IVRS provides full
therefore enhancing control and              visibility of released finished patient
reducing management concerns.                kits held in Sponsor, or third party
                                             depots, and also at the study sites.
A variety of different approaches are
available for management of the              During study set up, it is usually
supply chain when the study goes live,       decided to supply sites either by using
 The Clinical Trial Supply Chain – Before and After the Trial Start
                               Date

defined stock levels that are resupplied    strategies. In combination with IVR or
based on various set trigger points, or     in isolation, these can be effectively
by a just-in time delivery (for each        used upfront to help decide on actual
patient visit) depending on the best fit    site supply strategies. Forecasting can
for the study.                              also be used to estimate how long
                                            quantities of supplies will last for. This
Ultimately, this can assist the clinical    can be particularly useful when the
trial supply chain in not only              study has commenced and forecasts
presenting alerts for low stock levels at   need to be made covering the entire
sites, but also in country or central       supply chain for resupply of study kits.
depots such as a contract
packager/distributor. The ability to        Electronic Data Capture (EDC)
manage the supply chain at site,            systems in the supply chain
country depot and central depot allows
the trial medication to be managed          Although primarily for quality data
more effectively, and can assist in the     collection, certain data sets within
overall supply chain. Again, lead times     EDC systems can be used by
for all components (such as bulk drug)      distributors to predict an efficient just-
and production of supplied kits, means      in time drug supply, again helping
that careful monitoring of this interface   effective monitoring of inventory and
is required.                                reduction in waste drug. By using
                                            patient enrolment information and also
It has already been possible by             establishing specific dispensing visit
agreeing common data set protocols to       timetables, inventory can be managed
permit data interchange between IVR         between a distributor and EDC system.
and distributor systems to facilitate       In our experience, this approach can
electronic ordering of patient supplies.    work well for trials with simple
Although not full integration, it does at   dispensation rules and minimum
least serve to enhance reporting,           dosing scenarios.
visibility and ordering efficiency,
especially when integrated with bar
coding of the clinical supplies. By         Future solutions
utilising a vendor with both
distribution and IVR expertise, the trial   Several companies involved in
supply can be integrated with input on      outsourcing have attempted
streamlining trial set up and               successfully the process of data
management of drug inventory.               integration on specific parts of the
                                            supply chain. However the main issue
Forecasting programs                        remains that with so many differing
                                            in–house systems and services
Programs are available that can             provided by third parties that solutions
simulate different trial supply             tend to be point to point. As a result
scenarios and model the affect of using     Sponsor companies that use a suite of
differing variables in terms of patient     tools to manage the clinical trial supply
recruitment levels, the quantity of site    chain face multiple areas of data
shipments and multiple site supply          integration. Each of these requires
         The Clinical Trial Supply Chain – Before and After the Trial Start
                                       Date

     programming, testing and validation                   Conclusion
     for each source in the chain. Likewise,
     the vendors also will have this problem               Sponsor companies can assist the
     for each Sponsor Company they are                     clinical trial supply departments both
     involved with.                                        within their own company and
                                                           outsourcing partners, by planning
     However, this may not be the case in                  ahead and giving some visibility to the
     the future. Organisations such as                     drug development plans. This will
     CDISC (www.cdisc.org) are working                     assist in management of demand
     to establish guidelines for data transfer             forecasting and capacity, and also
     standards, which could provide a                      identify potential problems in advance.
     platform for future integrations. Also
     file transfer protocols, such as XML,                 Further use of technology to control
     offer enhanced possibilities for data                 and manage various parts of the
     transfer. Data portals that allow                     clinical supply chain means that data
     multiple sources to “speak” using an                  integration needs will grow within the
     integration layer present an                          industry. Organisations will strive to
     opportunity for automated data sharing                focus not only on operational
     between companies, therefore feeding                  expertise, but also on the ability to
     data from site, depot and the                         integrate into set data standards that
     manufacturing facility to allow tighter               allow them to take their place in an
     supply chain integration.                             integrated supply chain.

                                                           References:
  INVENTORY      VENDOR       IVRS           SITE/ DEPOT
  SYSTEM
                 INVENTORY                   INVENTORY     1: World-class clinical supplies, Drug
                                                           Information Journal
  BULK           MATERIALS
                              SUPPLY
                              STRATEGIES
                                             MATERIALS        Vol 31, pp 697-714, 1997
  DRUG           STUDY KITS                  STUDY KITS
                              STOCK LEVELS




              Data integration layer




Reports – automated supply management




     Figure 2- future data standardisation
     allowing automated supply chain
     integration

				
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Description: The Clinical Trial Supply Chain – Before and After the Trial Start