Items classified as biological materials can be derived from both humans and animals, such as blood, plasma, tissue, urine and feces samples. The material obtained via leukapheresis for the production of cell and gene therapies also falls into this category, as do biologic drug substances that are used to formulate final drug products, such as viruses and viral vectors. Finally, developmental drugs and vaccines that contain living cells and/or live/attenuated viruses and viral vectors are also considered biological materials.
The storage, handling and transport of biological materials require extensive knowledge about the properties and characteristics of the materials themselves and the conditions under which they can be safely stored and shipped. They also require comprehensive understanding of the local, national and international regulations for their transport and applicable customs requirements for each country involved.
Transport of these materials requires identification of appropriate primary and secondary packaging materials, compliant labeling, preparation of essential documents and knowledge of expected taxes, duties and other fees. Additionally, transport often requires managing a range of other considerations, given the temperature-sensitive nature of these materials and the often time-sensitive nature of the shipments.
Scheduling sample pickup and delivery necessitates coordination among multiple sites and identification of appropriate modes of transport. Real-time monitoring and tracking of packages are essential to ensure that they are handled appropriately, maintained at the correct temperature and successfully travel the desired route. Achieving visibility throughout the shipment process is also crucial for establishing a chain of custody and identity.
The use of quality management systems ensures compliance with Good Distribution Practice (GDP) for the transport, storage and distribution of biological with international quality and other requirements across the supply chain.
The FDA is expecting to approve 10–20 new cell and gene therapies per year by 2025.1 In addition to the Fast Track, Breakthrough Therapy and Priority Review designations available for traditional biologics, the Regenerative Medicine Advanced Therapy (RMAT) designation provides a further accelerated approval pathway for cell and gene therapies that treat disease states posing serious or life-threatening consequences.
Next-generation personalized medicines present additional challenges for logistics management. They must be stored and shipped at refrigerated (sometimes below –50 °C) temperatures. In many cases, biological material collected from a specific patient is processed and then returned to that same patient, which requires a secure chain of identity.
The FDA has published several guidance documents regarding the development, manufacturing and approval of cell and gene therapies. Given the complexity of the supply chain for personalized medicines and the need for end-to-end visibility, additional guidances are expected regarding the temperature-controlled logistics needed for these next-generation treatments.
A temperature-controlled supply chain enables storage, shipment and delivery of temperature-sensitive materials under refrigerated (or frozen) conditions without interruption. It requires scientific knowledge and understanding, the implementation of advanced packaging and information technologies and effective logistical planning capabilities. Key elements include suitably designed temperature-controlled packaging with incorporated real-time monitoring systems, refrigerated modes of transport and storage facilities, an effective quality assurance system and open and transparent communication and collaboration across the supply chain.
An unbroken temperature-controlled supply chain is essential to ensuring product safety, efficacy and quality for drug products and biological samples collected for diagnostic purposes or for use in the production of next-generation medicines. Continuous advances in technology are leading to improved product integrity and safety, increasing the efficiency of the pharmaceutical supply chain. This helps to ensure that the right biological materials are delivered at the right times to the right locations, and, for personalized medicines, to the right patients.
Regulations for the international shipment of biological materials originate with the International Civil Aviation Organization (ICAO). The Dangerous Goods Regulations established by the International Air Transport Association (IATA) are recognized by the ICAO as the field guide for practical reference by industry.2
Under these guidelines, biological materials fall into one of two categories within the classification division 6.2. Category A materials are infectious substances that contain pathogens that can affect humans or animals. These materials contain pathogens that are capable of causing permanent disability or life-threatening or fatal disease in otherwise healthy humans or animals.
Category B biological substances are infectious materials that do not meet the criteria for inclusion in Category A and do not cause life-threatening or fatal disease or permanent disability in humans upon exposure. These represent the bulk of pharmaceutical industry shipments. Some biological materials (typically patient specimens and blood for transfusions) with a minimal likelihood of containing pathogens are exempt from certain requirements.
The requirements for shipping Category B biological substances are outlined in IATA’s Danger Goods and ADR’s Packaging Instructions 650 (road) regulations. All materials must be packaged in a leak-proof primary container, with sufficient absorbent material in place around liquid materials to absorb the entire contents if the container should break. The primary container and absorbent must be placed in a secondary leak-proof container and surrounded by an outer rigid packaging material. It must also be appropriately marked as a Category B biological substance.
IATA’s Perishable Cargo Regulations (PCR) serves as a reference guide for all stakeholders involved in the packaging and handling of perishables for air transportation. Chapter 17 Air Transport Logistics for Time and Temperature-Sensitive Healthcare Products requires the implementation of a quality management system, service-level agreements and specific training. IATA created the Center of Excellence for Independent Validators in Pharmaceutical Logistics (CEIV) program to help organizations understand the requirements.
There are three main types of packaging solutions for temperature-sensitive biologic materials: active (dynamic), semi-active and passive (static).3 Active packaging relies on an external power source to maintain a constant temperature. In semi-active solutions, a static cold source, such as a phase-change material (PCM), is placed in an isolated compartment, and heat exchange between the biological material and the cold source is regulated using a system that operates without an electrical power source. Passive packaging comprises eutectic plates of a PCM within an insulating material.
Standard temperature ranges for the shipment of biological materials include deep-frozen (below –50 °C), frozen (–50 °C to –20 °C), refrigerated (4 °C to 8 °C) and room temperature (15 °C to 25 °C). The rapid development of next-generation medicines and increasingly strict regulations are driving the demand for higher-performance, smart packaging solutions that are fit-for-purpose across numerous supply chains, including those that extend into emerging markets.3
Today’s temperature-controlled packaging solutions are much more efficient and robust than traditional passive packaging that used chilled and frozen water surrounded by bulky insulating foams. The use of lightweight vacuum-insulated panels (VIPs) and PCMs provide greater reliability in a smaller space for increased payload efficiency. While they are more expensive initially, they have proven to be more cost-effective over the long term.3
Most of these packaging solutions also contain integrated data collection and transmission capabilities linked to web-based asset management software systems for real-time monitoring and tracking of the environmental condition (e.g., vibration, light, humidity, pressure, temperature, orientation) and location of a package as it moves through the supply chain. The data is not only used to ensure proper handling and delivery; historical information enables data-driven logistics decision making and can be leveraged to improve packaging design.4
Given the greater cost of these smart packaging solutions, there is a movement toward utilizing reusable systems. The asset-management software systems are thus also being leveraged to facilitate reverse logistics.3
An effective logistics provider must be aware of the critical nature of all biological samples and be able to supply the appropriate packaging to meet any temperature requirements, identify optimal shipping lanes and confirm import and export requirements. They must also have the infrastructure available to ensure the integrity of these shipments from the moment they are packaged and depart the site through to final delivery.
Yourway has the biological, warehousing and logistical expertise and capabilities to meet customer needs for temperature-controlled storage and 24/7 package pickup with no weight, size or value restrictions.
Yourway does not, however, simply offer logistics, warehousing and packaging support. At Yourway, we take an integrated solutions management approach, leveraging our experience and expertise to provide an array of customized solution-based offerings, including project management support, planning and optimization guidance, comparator sourcing, ancillary supply sourcing, forecasting and returns/reconciliation management. We offer highly customized solutions that ensure high-quality, responsive, tailored support from start to finish.
Yourway’s temperature-controlled transport specialists enable the shipment of phase I, II, III, and IV materials, finished goods and production raw materials. Over the last five years, Yourway has substantially expanded our international resources and global network to be closer to clients and to provide them with even more responsive global service. Our experienced network of agents and associates located around the world clear and deliver shipments to their destinations as soon as they arrive. Yourway is also committed to facilitating reverse logistics, including reclamation and value recovery, returns and reconciliation and, where appropriate, storage, consolidation, destruction or disposal.
Yourway’s worldwide service also includes documentation support and the provision of regulatory advice regarding country-specific requirements. Customs fees are managed proactively and paid by Yourway, regardless of the cost — shipments are never held up waiting for the client to pay fees. Overall, Yourway’s proactive management approach helps our customers avoid delays of all kinds during the shipment of critical clinical trial materials.
Gulam Jaffer is President of Yourway, an integrated biopharmaceutical supply chain solutions provider offering a full range of primary and secondary clinical packaging, comparator sourcing, logistics, storage and distribution services for the global pharmaceutical and biotech industries. Headquartered in Allentown, Pennsylvania, with additional strategic locations worldwide, Yourway specializes in time- and temperature sensitive clinical drug product and biological sample shipments. Yourway is a flexible and reliable logistics partner committed to the safe, efficient and on-time delivery of clients’ high-value, high-priority clinical materials.
For more information on Yourway, view the Company Profile.