Defining the challenges
As the number of clinical-trial sites expands on a global basis, several challenges arise in managing on-time CTM delivery.
"The use of technology to track delivery and inventory is critical," says Frank Lis, vice-president and general manager of
clinical-supply services with Catalent Pharma Solutions. "Because some studies involve many countries, investigators, and
depots, you need tools to help track shipments and inventory."
Others agree. "A key factor is the management of a depot/site network," says Jim Curry, president and CEO of OpStat, a consultancy
specializing in supply-chain management, lean manufacturing, and inventory management. "There needs to be accurate and timely
management of inventory information from those involved in the clinical supply chain, including from third-party logistics
providers." Managing CTM supply requires that information on CTM be created and maintained accurately. "Problems can arise
in entering or omitting data in inventory systems or interactive web response systems (IWRS). IWRS collect and provide access
to clinical-trial study data. "Such errors may, for example, relate to the number of patients in a trial at a given site,
level of patient recruitment, the level of patient dispensing, or other entry errors that affect the dose requirements at
a given site, which in turn, affect the CTM supply chain," says Curry.
When expanding the number of sites globally, additional challenges may arise. "Import and export permits are a challenge with
some countries," says Lis. "You need to make sure all documentation is completed well in advance and that permission has been
received to ship products into these countries." Once documentation and permission are received, the transport and storage
of product, particularly temperature-sensitive ones in a cold chain, are crucial. "In some countries, transportation and storage
of controlled-temperature products are difficult," says Lis. "Some of the investigators are not near major cities and have
little experience with conducting studies and handling product."
Resolving the challenges
In addressing these challenges, experts offer various approaches to mitigate problems of on-time delivery and to align supply
with demand at clinical sites. "Senior management must first have the vision to recognize the importance of the supply chain
and to recognize that appropriate tools are needed to effectively manage the supply chain," says Curry. "Even for emerging
pharmaceutical companies with few drugs entering Phase II and Phase III trials, the complexity grows fairly quickly in terms
of levels of patient enrollment, the number of sites, various dosing schemes for a clinical product, and the related need
to meet CTM supply requirements. A formal monthly demand and operations planning process that includes the supply-chain, clinical,
manufacturing, quality, and R&D functions is important to synchronize the entire chain," he says.
Simulation and modeling
. Effective modeling of study forecasts, along with dynamic inventory projections, to predict and modify CTM supply is key,
says Curry. He identifies several best practices for effective CTM supply management:
- Perform modeling of clinical study forecasts before initiation and re-forecasts as clinical studies are started to determine
the latest projections for all studies for a given molecule.
- Include study-design arms, site activation, and patient-recruitment levels in study forecasts.
- To determine supply requirements for some drugs, depending on the study design and disease, project patient time in a study,
including deactivations (i.e., patients withdrawing from the trial) and extensions because both affect the amount of supply
required.
- Construct and analyze study forecasts for all clinical studies back to API manufacturing.
- Implement protocols and practices to determine reasonableness of data and for detecting omission of data from clinical sites,
which includes the ability to easily adjust for errors.
- Use capabilities for extensible markup language (XML) to make data available for electronic data-capture systems, IWRS, third-party
logistics providers, and manufacturers.
- Have a four-year horizon for finance projections (i.e., assuming that most studies are approximately two years in length)
for R&D. Although these projections may represent a major investment for large and small pharmaceutical companies, it is strategically
important to have such information in place to predict CTM supply.
Curry offers an example of how such a simulation model works in practice. The simulation model is integrated with spreadsheet
input and output capability to manage the flow of materials through all phases of the CTM supply chain. The manufacturing
processes for APIs, drug product, packaged product, and patient kits are included in a synchronized flow. Inventory may be
monitored at each point in the chain, and replenishment rules are established for each plant or work center involved.
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