Each contract or internal manufacturing site may be modeled to the level of detailed required. A high level model of the flow
includes the capability to drill down to identify time slots when production will be required based on contracted lead times.
When the model is run, graphics and metrics are available that may be selected as needed. For example, the timing of batches
and lots in the production flow are displayed from drug substance to drug product to packaged products and kits. It also is
possible to measure how long kitted product has been in the clinical-trial pipeline because each lot is time-stamped as it
goes through each process. "Monitoring expiration dates for CTM supply is crucial as the administration of clinical trials
may be delayed or adjusted based on clinical results," says Curry.
The demand for patient kits is based on the patient recruitment rate for the clinical-trial, and the usage is based on the
study design for the trial. Usage is calculated based on the size of kits, which dictates how long a kit will last and when
re-orders from patients will be required. In addition to the normal duration of the trial for each patient, the patient deactivation/extension
rate also is factored into the model.
. Managing the CTM supply chain when cold-chain requirements are involved requires additional knowledge, skill, and technology.
Dan Gourley, director of global clinical logistics with Catalent Pharma Solutions, gave insight into the factors to consider
by providing a cold-chain supply-management case study at a recent conference (5). The example he offered was a Phase III
medicinal product, which was packaged in the US, but shipped to multiple countries and depots. In this particular example,
the product was required to be maintained at temperatures from 2–8 °C. Large kit sizes required large shipping volumes, and
active and passive shippers were used, depending on the application. An active system refers to a system that maintains temperature
through battery-powered refrigeration. A passive system refers to a system that maintains temperature through the use of refrigerated
and frozen gel combinations.
In developing the appropriate cold-chain logistics and supply-chain management of the product, Gourley noted several key areas
Security by protecting the product against damage, loss, or theft while en route or upon arrival
Maintenance of cold-chain conditions in the air and on the ground
Planning, adaptability, and contingency plans to ensure supply continuity
Required documentation, including country-specific documentation
Regulatory compliance to ensure correct valuation of material to decrease any risk of potential delays with countries' regulatory
Improvements in kit design to enable smaller, lighter, and cost-effective packaging
- Real-time assurance by using technology-enabling tracking of temperature and location.
In managing the CTM supply chain, both country-specific and clinical-site-specific requirements, which include potential depot
needs, must be considered. Gourley emphasized that it is important to review the capabilities and capacity of depots receiving
cold-chain materials. Issues to consider are country-specific restrictions, the capacity of the depot to store the supplies,
and the type of shipment package that the depot can handle. Shipment packages can be active, passive, or phase-change. Phase-change
shipments refer to reusable shipping systems.
He also emphasized the importance of reviewing country-specific regulations for import, such as import permits or licenses,
special packaging and labeling requirements, and physical pack-out of materials. Custom valuation is another important factor
to consider when shipping supplies. Custom-valuation methods typically for clinical supplies include four types: the transaction
value; the transaction value of identical or similar merchandise (i.e., based on the transaction value of previously imported
merchandise); deductive value (i.e., the selling price in the US less certain post-importation costs); and computed value
(i.e., foreign-supplier cost information for materials, processing, profit, and general expenses). To mitigate risk with respect
to custom valuations, Gourley stressed the importance of receiving input from the finance, procurement, and legal departments,
documenting the method of calculation, having shipping documentation reviewed by a customs broker or consignee before shipping,
and ensuring that all import license requirements have been completed.