The Clinical Trial Supply chain: Best practice to ensure

effective management.

Clinical trails are getting larger and more complex, have ever shrinking timeframes
and now reach the four corners of the globe, it therefore comes as no surprise that
problems arise between the many different organisations involved, client, vendor and
sponsor.

All involved have a distinct common goal in terms of reaching the effective trial start
date and ensuring that each patient and site is supplied with the correct medication at
the right time.

The use of critical path planning in Clinical trial supplies can lead to bottlenecks in
availability, with the associated knock on effect on cycle times for getting new drugs
to market. There are a number of best practices and tools that can be used both before
and during the trial to ensure that the clinical supply chain is managed more
effectively and operates more efficiently.

Working backwards; effective planning reduces the use of the crystal

ball.
It is vital that Sponsor companies should have a plan of activities; this should not be a
crystal ball exercise. Lead candidates and pipelines for each year are usually known in
advance and this information, if shared and used correctly, can lead to effective
forecasting of demand and production. Working backwards from the clinical trial
start dates means that lead times can be identified for all processes, including shipping
to the study sites, appropriate storage of completed and released supplies, packaging
and labeling of supplies, material requirements for packaging and labeling and the
production and supply of bulk IMP

Acting on this information can enable effective pre-planning, and can help all
involved identify potential problems, bottlenecks and solution.

Often, the actual required start date for trial activities has already passed. It is useful,
when preparing the protocol for the clinical trial, that the Clinical teams plan a time
point when individual clinical supply requirements are “frozen”. This allows the
ticking clock for trial start date to be reset after any alterations to the set supply
requirements. Examples for this are primary packaging, kit formats, required
quantities and label text. The clinical supply chain must be seen as a global one –
from raw materials right through to world-wide distribution to the patient.
 Clinical Supply Inventory Chain

BULK IMP

Site inventory
CENTRAL
Packaging
PACKAGED
components
TRIAL SUPPLY
STOCK
Depot inventory
Label text

Trial FPI date Resupply – trial running

Figure 1- Working back from expected First Patient In (FPI) Date

When an overview of all scheduled trial supply requirements is agreed, the planning
process can enter into a more detailed phase noting each 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
submissions and approvals, along with country specific requirements, in parallel with
the production of the clinical trial supplies and its associated inventory chain.

Stock levels and tracking of clinical trial supplies

Once the clinical trial supplies are available to start the trial, the tracking and
monitoring process can begin to ensure that stock levels of kits are maintained and
that the supply to each patient is continuous and uninterrupted. Usually for later phase
trials with large patient populations, supplies are delivered in phased campaigns, often
due to expiry date limitations or comparator availability. This in turn means that
stock levels of the initial supply of kits become absolutely critical to continuous
patient supply. Now we enter a crucial phase.

After study initiation, monitoring of clinical supply inventory throughout the supply
chain is essential in order to monitor study kit usage and available stock levels, ensure
the drug is always available for patients, minimise waste medication, alert sites in
case of potential supply delays and comply with GMP/ GCP conditions .
Approaches to clinical trial supply management: tips for
improvement

Monitor stock level data

Once a trial starts and recruitment gets into gear, supply stock levels can often start to
deplete at a different rate than expected. Add to this the needs of expiry date
management and soon supplies can start to dwindle. It is essential that stock level data
is monitored throughout the entire supply chain, but due to multiple parties and
systems involved this is not a straightforward process.

Some large Sponsor companies have inventory and management systems capable of
monitoring various portions of the supply chain. When the decision has been made to
outsource portions of the supply chain, Sponsor companies can suddenly find a
gaping hole in any materials management systems. In many cases, once shipped
globally, supplies can disappear totally from the Sponsor’s radar, therefore creating a
reliance on unconnected reports from other systems (mostly 3rd party), which require
manual manipulation of data to forecast future supply needs and manufacturing
requirements.

Meet with sponsor companies and vendors

It is useful to note that as kit inventory is monitored by whatever means selected by

the Clinical Managers, plans must be included to make the information available to
each participant in the supply chain. This means that outsourcing partners need to be
involved in relevant data exchanges that may affect the availability of additional
supplies, and that this involvement occurs in a timely fashion. In our experience, joint
meetings involving Sponsor companies and associated vendors prior to study
commencement are invaluable. Such meetings can present a platform to examine
interface exchanges and possible alternative approaches to the study design. Also, it is
possible to have one vendor responsible for multiple areas of the supply chain,
therefore enhancing control and reducing management concerns.

Supply chain management

A variety of different approaches are available for management of the supply chain
when the study goes live, but the Trial Supply Manager must link the inventory data
back into the complete chain. Examples of inventory management include:

The manual approach

Many Sponsor companies employ a manual approach to the supply chain. Generally
this will mean pre-defining set amounts to ship to each site on activation and then
another set amount for further supplies. This can result in reduced visibility of the
inventory and provide difficulties if sites take on a different level of activity than
predicted. Supplies are usually manufactured/ packaged with at least of 100%
overage, therefore adding to the trial cost and lead times for production. Study
monitors can provide inventory verification but this approach can lead to a
fragmented approach if multiple supply campaigns are required.

Use of Interactive Voice Response Systems (IVRS)

Traditionally both IVR, and similar web based systems have been the scope of large
Phase III trials, with complex dosing and inventory requirements. However the
quality of reporting tools available and management of randomisation has encouraged
increased use within the industry. An IVRS provides full visibility of released
finished patient kits held in Sponsor, or third party depots, and also at the study sites.

During study set up, it is usually decided to supply sites either by using defined stock
levels that are resupplied based on various set trigger points, or by a just-in time
delivery (for each patient visit) depending on the best fit for the study.

Ultimately, this can assist the clinical trial supply chain in not only presenting alerts
for low stock levels at sites, but also in country or central depots such as a contract
packager/distributor. The ability to manage the supply chain at site, country depot and
central depot allows the trial medication to be managed more effectively, and can
assist in the overall supply chain. Again, lead times for all components (such as bulk
drug) and production of supplied kits, means that careful monitoring of this interface
is required.

It has already been possible by agreeing common data set protocols to permit data
interchange between IVR and distributor systems to facilitate electronic ordering of
patient supplies. Although not full integration, it does at least serve to enhance
reporting, visibility and ordering efficiency, especially when integrated with bar
coding of the clinical supplies. By utilising a vendor with both distribution and IVR
expertise, the trial supply can be integrated with input on streamlining trial set up and
management of drug inventory.

Forecasting programs

Programs are available that can simulate different trial supply scenarios and model the
affect of using differing variables in terms of patient recruitment levels, the quantity
of site shipments and multiple site supply strategies. In combination with IVR or in
isolation, these can be effectively used upfront to help decide on actual site supply
strategies. Forecasting can also be used to estimate how long quantities of supplies
will last for. This can be particularly useful when the study has commenced and
forecasts need to be made covering the entire supply chain for resupply of study kits.
Electronic Data Capture (EDC) systems in the supply chain

Although primarily for quality data collection, certain data sets within EDC systems
can be used by distributors to predict an efficient just-in time drug supply, again
helping effective monitoring of inventory and reduction in waste drug. By using
patient enrolment information and also establishing specific dispensing visit
timetables, inventory can be managed between a distributor and EDC system. In our
experience, this approach can work well for trials with simple dispensation rules and
minimum dosing scenarios.

Future solutions

Several companies involved in outsourcing have attempted successfully the process of

data integration on specific parts of the supply chain. However the main issue remains
that with so many differing in–house systems and services provided by third parties
that solutions tend to be point to point. As a result Sponsor companies that use a suite
of tools to manage the clinical trial supply chain face multiple areas of data
integration. Each of these requires programming, testing and validation for each
source in the chain. Likewise, the vendors also will have this problem for each
Sponsor Company they are involved with.

Standardised data transfer?

Organisations such as CDISC (www.cdisc.org) are working to establish guidelines for

data transfer standards, which could provide a platform for future integrations. Also
file transfer protocols, such as XML, offer enhanced possibilities for data transfer.
Data portals that allow multiple sources to “speak” using an integration layer present
an opportunity for automated data sharing between companies, therefore feeding data
from site, depot and the manufacturing facility to allow tighter supply chain
integration.
 INVENTORY VENDOR IVRS SITE/ DEPOT
SYSTEM
INVENTORY INVENTORY

SUPPLY
BULK MATERIALS MATERIALS
STRATEGIES
DRUG STUDY KITS STUDY KITS
STOCK LEVELS

Data integration layer

Reports – automated supply management

Figure 2- future data standardisation allowing automated supply chain integration

More efficient and effective clinical trials?

Sponsor companies can assist the clinical trial supply departments both within their
own company and outsourcing partners, by planning ahead and giving some visibility
to the drug development plans. This will assist in management of demand forecasting
and capacity, and also identify potential problems in advance.

Further use of technology to control and manage various parts of the clinical supply
chain means that data integration needs will grow within the industry. Organisations
will strive to focus not only on operational expertise, but also on the ability to
integrate into set data standards that allow them to take their place in an integrated
supply chain.

Jonathan Calderwood
Global Marketing Manager
Almac Clinical Services, Craigavon, UK
Tel: +4428 3836 2436 Fax: +4428 3836 3623
E-mail: jonathan.calderwood@almacgroup.com