The developments reshaping the clinical trial landscape are wide-ranging. They include the diseases that researchers are targeting, the types of products being developed, and how and where development is taking place. These change-makers include:
- the explosion in the development of cold chain products and expanding use of temperature-controlled shipments
- the growing focus on and success of research efforts in therapeutic areas such as cancer, Alzheimer's disease, and rare and orphan diseases
- continuing globalisation of trials and the impact of supplying increasingly remote clinical sites
- ever-changing importation regulations and documentation requirements
- escalating demand for comparator alongside the need to prevent counterfeit products from entering the supply chain
- the emphasis on patient-centricity and interest in the potential of direct-to-patient studies
- emergence of what could be characterised as an 'Amazon-like' culture of immediacy, reflected in 24/7 communication and response
- the need for flexibility and contingency planning in what is an increasingly crisis-stricken world.
Supply chain logistics are estimated to account for as much as a quarter of total annual pharmaceutical R&D costs, a price tag that is projected to grow.
While multiple factors are responsible for changing trial logistics, the explosive growth of biologics is the primary driver. With cold fast becoming the new normal, cold chain management is emerging as a major concern for biopharmaceutical companies, and for good reason. By 2020, more than half of bestselling drugs will be cold chain products. A major contributing factor is the growth of the global biosimilars market, which could reach $35 billion by 2020.
Maintaining a secure cold chain through the storage, handling and transportation of temperature-sensitive drugs ensures product quality and integrity, and compliance with existing regulations, guidelines and codes. As the number of cold chain products increases, so does regulatory interest in cold chain handling.
Governments and industry alike are updating cold chain rules and expanding the scope of temperature monitoring and control. Shipping products, regardless of whether they need to be maintained at cold temperatures, is a costly part of drug development. Packing and transporting temperature-sensitive materials, and demonstrating by process qualification or measurements that shipments remain within the required temperature parameters, add another layer of complexity to logistics. And, of course, complexity drives up costs.
In 2018, logistics for cold chain products are expected to cost drug makers $14.4 billion. By 2020, the price tag is projected to reach $16.7 billion. In addition to air, parcel and truck service, this includes the costs of specialised tertiary packaging and instrumentation such as insulated boxes, blankets, phase-change materials, active temperature-control shipping containers, and various temperature sensors and recorders.
Meanwhile, an increasing number of products are being transported under colder conditions. Regulatory authorities are demonstrating a preference for shipping all drugs under controlled temperature conditions. One reason for this is differences in interpretation among countries about what constitutes ambient conditions.
As a result, sponsors are beginning to ship even ambient drugs, such as capsules and blister packs, under controlled temperatures accompanied by temperature monitors. In addition, there is movement towards shipping temperature-controlled products in a frozen state.
In an effort to control costs, the biopharma industry is seeking more economical shipping methods for safely transporting cold chain products to investigator sites across the globe. These efforts include exploring new packaging and technology. In 2016, Fisher Clinical Services partnered a sponsor on a pilot programme using a high-performance, phase change material (PCM) reusable shipper. The pilot was used for several studies in Europe and the US.
Reusable shippers offer many potential benefits over single-use ones. For one thing, reusable shippers can increase the temperature-controlled lifespan to 96 from 48 hours of single-use shippers. In addition, reusable shippers have been shown to reduce temperature excursions and allow more level load shipping. The advantages for investigator sites include a reduced burden of disposal and less impact on the environment.
Fisher Clinical Services worked closely with the sponsor to establish performance indicators for the pilot. The agreed-upon indicators included a shipper return rate of more than 90% and positive feedback from investigator sites. Investigator sites have long expressed frustration about the need to store and dispose of single-use shippers and concern about the waste such shippers generate.
The pilot was a resounding success. In addition to resulting in a lower temperature excursion rate and greater contingency for delays than traditional, single-use shippers, the reusable shippers were lighter and cheaper to transport.
While more expensive, the reusable shippers compensated for their higher price tag by significantly reducing waste and environmental impact.
In addition, the 97% return rate exceeded the target. Investigator sites reacted enthusiastically, citing the reduced burden and expense of shipper storage and disposal.
The project team estimated that the use of reusable shippers would divert 300,000lb of waste from landfill in year one, with a targeted reduction of 1.2 million pounds diverted from landfill in year two.
Within ten months, the pilot programme was declared effective at meeting all objectives and the reusable shippers were adopted as standard.
Begin planning early. The ideal time to begin discussing supply logistics is while the protocol is under development, rather than after it has been approved. While that might appear premature, it isn't. Early planning offers maximum options. Having the time to explore and consider all options, particularly for cold chain shipments, can preserve resources and prevent headaches once the trial is under way.
Take the time to identify vulnerabilities. Ask questions and brainstorm potential logistical problems with the clinical team and a trusted supply chain partner. Spend time identifying the areas that may require special attention, and identify means of addressing such issues should they arise.
Opt for maximum flexibility. Build the vulnerabilities that were identified - the 'what ifs' - into logistical plans. For those who aren't convinced this is necessary, ask how often anything has ever gone exactly to plan. In a world in which crises of varying severity occur daily, the ability to pivot rapidly is critical.
Select the right partner. Choose a supply chain partner with the knowledge, experience, breadth of services and global footprint necessary to address vulnerabilities with flexible solutions.
If possible, seek out a partner capable of addressing the unique nuances of clinical trials across the world. Work with cold chain specialists with excellent track records for handling high volumes of cold chain clinical supplies and distributing them to remote areas of the world.
Err on the side of safety. Forecasting is a critical tool for the purpose of managing limited resources and preventing waste. However, running out of materials can be more expensive than investing in some overage at the beginning of a trial. While no one advocates wasting costly biological drugs, experience has demonstrated that some overage is necessary in every trial. Consider overage to be a form of insurance against the 'what ifs'.
Finally, it's worth remembering that clinical trial logistics are aimed at ensuring that the correct drug reaches the intended patient at the right time. Conducting a trial comes with a commitment to serve trial patients by putting their safety and well-being first.
Honouring that commitment in every trial ensures that everyone wins - the sponsor, the investigator sites and, most importantly, the patients.