Rachel Griffiths, PCI, advises on maximising clinical supply chain efficiency for biologics
Rachel Griffiths, PCi
The supply chain requirements of a biological product are not significantly different to those of a non-biological product; deliver the drug safely and on time, to the right location, at the right temperature and at the lowest cost. Expertise is essential in achieving these requirements.
Biologics are a preparation, such as a drug, a vaccine or an antitoxin, which is synthesised from living organisms or their products and used as a diagnostic, preventive or therapeutic agent. These products usually require cold chain storage, packing and distribution; some may require ultra low temperature (ULT) storage and logistics. Maintenance of the product at the correct temperature is critical and must be managed throughout the supply chain.
The supply chain for low-temperature biological investigational medicinal products (IMPs) can be considered in three phases.
The importance of forward planning
In the EU, IMPs for use in clinical trials must be stored and distributed from a licensed facility in compliance with good manufacturing practice (GMP) and good distribution practice (GDP). In the majority of clinical trials, the IMP is not manufactured in the same country as the qualified person (QP) certification and requires importation. For biological products, the information required to obtain import licenses can be lengthy.
In the UK, the Department for Food, Environment and Rural Affairs (DEFRA) issues licences for the import of any animal or human derived product. Issues occur if the product contains materials not covered under general licences, as individual product applications must be made. It is vital at the initial set up of a clinical trial, those responsible obtain all the details of the IMP to import into all countries where the trial is taking place and establish timelines for obtaining import licenses. This information may influence the decision to perform the trial in a country and should be considered alongside the regulatory authority requirements.
The transportation method is also important when shipping biological products. Most require cold chain and are shipped by air, as the time product temperature can be maintained during transit is limited. The shipping systems must maintain the required temperature for the expected duration of the flight, customs clearance and delivery. In most cases, specialist couriers are used and have the capability to hold the material at 2–8°C or top up dry ice at the airports. These specialist shipments can be costly; however, the risk of losing a shipment owing to a temperature excursion far outweighs these costs, as most biologics are far more expensive than conventional drugs.
Mapping shipping routes and storage depots
When shipping to countries outside of the EU, several factors may require the use of an in-country depot. These factors include import license requirements (an import license is required for each shipment) and transportation time. Additionally, for some trials, the time between patients being screened to receiving their first dose can be short, customs processes make it impossible to meet these timelines and depots are essential.
The supply route should be considered on an individual product and country basis. The product, cost and availability as well as site storage capacity and recruitment rates must be addressed to ensure a secure and cost-effective route that meets the trial demands.
Cold chain packaging for trial material logistics
The selection and preparation of shippers is critical for temperature-controlled products. The shipper must be qualified to last the duration of the shipment and the courier should have the facilities to top up dry ice or hold refrigerated product.
Even when shippers are qualified, a temperature monitor must be included to ensure the product remains within temperature. Temperature monitors are available with a USB connection, allowing immediate review of the data. These monitors are usually single use, which also reduces cost. Whilst high-quality shippers and monitors may add additional cost, using them reduces the risk of temperature excursion.
These phases look at the supply chain for a product where final packaging is already defined. Greater efficiencies could be made if an integrated design process is introduced in conjunction with the supply chain.
By setting up an integrated design process in which the whole supply chain is considered at the design or proposal stage, a streamlined, well-documented and efficient strategy for each trial and product can be developed that is capable of delivering product on time, at temperature and cost effectively.
Selecting an experienced service provider to work with early in the study development phase ensures frustrations common to shipping cold and ultra-cold chain products can be avoided. This allows clients to focus their energies on the successful delivery of their lifesaving therapies.