In biopharmaceutical development, ancillary business operations such as shipping logistics are frequently perceived as secondary to the ultimate goal of discovering novel treatments and cures for the world’s most devastating diseases. This is especially true today as large pharma is coping with expiring drug patents and dwindling product pipelines. However, in the hypercompetitive world that is drug development, forward-thinking companies have found that optimizing their clinical trial supply chain operations can provide a strategic advantage to accelerating current and future drug discovery.

Pharmaceutical companies are conducting more clinical trials than ever. The rising costs, complexity and regulatory hurdles caused by the increasingly global nature of these clinical trials present significant challenges for companies seeking to effectively manage their clinical trial supply chain. Biomedical research is generating a growing amount of temperature-sensitive biomaterials that must be properly transported between collection sites, analytical labs and storage facilities. I will highlight measures pharma and biotech companies can implement to ensure the on-time, compliant transportation of temperature-sensitive clinical trial samples and supplies. The article will highlight:

• Packaging techniques to ensure biomaterial payload remains at pre-determined temperatures
• Global regulations that impact how temperature-sensitive biomaterials are transported
• The importance of chain-of-custody in meeting regulatory compliance
• The growing role of outsourcing as part of global cold chain strategies 

Packaging Techniques for Temperature-Sensitive Biomaterial Payloads

Temperature-sensitive biomaterials, such as clinical trial samples, cell banks, tissue samples and active pharmaceutical ingredients, play a vital role in bringing new drugs to market. As clinical research continues to expand into global initiatives, requiring transportation across multiple continents, packaging systems have become more sophisticated to correspond with the demand for tighter temperature control and prolonged delivery times of these materials.

Validated packaging solutions, in concert with industry-approved packing techniques, can help to safeguard materials in transit. For example, dry ice nuggets can be used to minimize air gaps. For liquid nitrogen shipments, the shipper must utilize properly validated dry shipper canisters. Prior to packaging samples into dry shippers, they must first be properly charged in accordance with the manufacturer’s instructions. Also, to avoid compromising the sample integrity of refrigerated biological materials that must be maintained at 2° to 8° Celsius, packaging must be properly pre-conditioned before shipping. 

Global Regulations

From a regulatory perspective, receiving and transporting temperature-sensitive biomaterials can be a challenge for companies that conduct clinical research internationally. Therefore, it is paramount that individuals who ship these materials be accustomed with regulations and guidelines that may effect their timely transport. 

The U.S. Department of Transportation (DOT) Hazardous Materials Regulations (HMR) and International Air Transport Association (IATA) Dangerous Goods Regulations (DGR) specify requirements for the safe transportation of hazardous materials by rail car, aircraft, shipping vessel and motor vehicles. These regulations dictate specifications for classification, packaging, hazard communication, shipping papers, incident reporting, handling, loading, unloading, segregation and movement of hazardous materials. Fines and shipping delays often result from lack of compliance with HMR regulations.

Customs regulations in emerging regions such as Brazil, Russia and China are also complex and strictly followed by customs staff. Any issues with the shipment itself, or the accompanying paperwork, can result in material being held in customs for prolonged periods. As such, it is essential to have a strategy in place to avoid these issues. For example, due to possible delays in completing customs requirements, temperature-sensitive material may be consigned with a courier that is capable of replenishing refrigerant in the event of a delay. Selection of a courier with capabilities in the region is critical. As much as three additional days’ worth of refrigerant may be recommended for shipments in cases where customs clearance may be difficult.

Establishing Chain-of-Custody

At various phases in drug development, biomaterials are often transported among collection sites, analytical labs and biobanking facilities that can be located in several geographical regions. As a result, establishing chain-of-custody can be a demanding practice. However, the process of verifying who has possession of valuable biomaterials can be streamlined if an organization outlines chain-of-custody guidelines in its Standard Operating Procedures (SOPs). These processes and procedures ensure uniform application of best practices and successful knowledge transfer. SOPs should be incorporated into routine training programs and be regularly updated to ensure compliance to an expanding array of regulatory requirements. 

An essential component to establishing a comprehensive chain-of-custody is a complete audit trail. Audit trails can be required by various regulatory agencies to help establish that materials have not been compromised while in transit or in storage. For a comprehensive audit trail, records should form a complete history of the specimens’ lifecycle and include:

• The type of specimen, such as tissue, blood or plasma
• The donor and location where the specimen was collected
• Date the specimen was obtained
• Storage and shipping conditions of the specimen at all times
• The final destination of the specimen

The demands for regulatory compliance, documentation, audit trails and material integrity have made validated chain-of-custody procedures a necessity to ensure the integrity of biomaterials for present studies as well as for future analyses. This will require organizations to be capable of reporting chain-of-custody processes through all stages of a specimen’s lifecycle. Personnel should follow these processes whenever specimens and their associated data are collected, transferred, stored, analyzed or destroyed. This is especially important today, as the recent focus on molecular therapies, personalized medicine and biomarker discoveries has placed an increased emphasis on quality biospecimen samples. 

Labels and Documentation 

Rigorous demands from authorities and industry associations worldwide necessitate SOPs be set in place not only for shipping, but also for labeling and documentation. Any controlled transport storage conditions, as well as warning statements or content identification, should be clearly stated on the label applied to shipping containers. Labeling must comply with IATA guidelines, be securely attached and clearly state that materials are to be transferred to a specified storage temperature upon receipt. 

Temperature Tracking and Monitoring 

Beyond selecting the proper packaging, logistics personnel can use temperature-tracking devices to monitor the temperature of their shipments. When stringent and detailed tracking is required, reusable data loggers can be placed inside the packaging to monitor temperature and time continuously. This data can be downloaded for graphing, reporting and inclusion in audit trails. If temperature excursions outside the predetermined temperature range occur, they should be evaluated and documented by logistics personnel. As an SOP, corrective action should be implemented when necessary, and documented. Clear directions should be provided to the recipient for the evaluation or disposition of the indicators and products. 

The Growth of Outsourcing

As I’ve outlined, maintaining a reliable, cost-efficient cold chain, one that both meets necessary regulations and also provides a competitive advantage, can be extremely challenging and time-consuming. For this reason, pharma organizations are increasingly turning to providers to manage these processes. Outsourcing these complex functions allows drug developers to mitigate risks and to allocate capital and resources to their primary mission of novel drug development. In addition, many companies have found that with the right expertise, an organization can increase its ability to fully leverage supply chain efficiency and incorporate cold chain strategies into its existing business models. To determine if outsourcing is the best course for a company, the following questions should be asked:

• Is our company qualified in cold-chain logistics and storage?
• Where would our resources be best allocated?
• Do we have the personnel to sustain insourcing?
• Do we have the resources to sustain insourcing?
• What would we gain from outsourcing? 

If outsourcing is considered to be the best option, companies should use due diligence. The ideal partner must demonstrate proven strategic expertise to ensure that temperature-sensitive samples and specimens do not degrade during packing, shipping, processing and storage. Critical services and capabilities that should be included in the evaluation of a partner include:

• Processes and systems that continuously monitor and track sample movement, handling and storage
• End-to-end logistics management services, including planning, on-site supervision and packing, regulatory compliant packaging, shipping, tracking, delivery confirmation and audit trail recording for each individual sample or specimen
• IATA certification to ship dangerous goods and infectious substances
• Partnerships with reputable couriers and leading worldwide ground and air transportation carrier
• Mobile logistics and transition management teams that can package and ship samples between any locations
• Emergency short-term or long-term storage and transition services
• Specialty in transportation regulations from U.S. Customs, DOT and foreign countries
• Dedicated, reserved biorepository storage space that can be utilized in the case of emergency sample relocation

Maintaining the cold chain from clinical site to final destination is vital but can be extremely challenging. Materials must be stored within a very narrow temperature range; temperature excursions, scarce resources and long travel distances can lead to a break in the chain. Pharma and biopharma firms must maintain logistic processes that keep pace with the globalization of clinical trials. They must monitor the quality and effectiveness of the supply chain and always be aware of new, innovative solutions that may provide a stable and reliable opportunity to minimize the risk in cold chain transport and improve cost efficiencies.

Russ Hager is senior director, Global Biorepository Operations at BioStorage Technologies. He can be reached at 866-697-2675 or russell.hager@biostorage.com.