Originally published on Outsourcing-Pharma.com.
The composition of clinical trial pipelines is changing quickly as the rise of advanced therapies adds another layer to the multi-decade shift from small molecules to biologics. This change is fueling once-unimaginable advances in the treatment of cancers, rare diseases and other conditions, but it is also placing strains on infrastructure and processes originally created to handle more robust small molecules. In this new environment, clinical drug distribution is a key enabler of success.
The significance of distribution has risen in line with the complexity of therapeutics and clinical trial designs. Whereas once clinical supply chains took robust small molecules to centers in North America and Western Europe, today they ferry expensive, highly-sensitive biologics to sites around the world.
Antibodies and other temperature-sensitive biologics account for almost two-fifths of the biopharma industry pipeline, up from around one-fifth 20 years ago.1 A fast-growing and vitally important part of the pipeline is made up of gene, cell and other advanced therapies that are even more sensitive and challenging to ship than antibodies.
As of the end of 2018, there were more than 1,000 active clinical trials of regenerative medicines, such as cell and gene-based therapies, according to the Alliance for Regenerative Medicine.2 That represents an increase of 63% over the past three years.13 The rise is underpinned by a 132% surge in the number of regenerative medicine trials targeting cancers.
There are reasons to think the growth will continue. Growth in Phase I trials has outstripped other stages of human testing, meaning the sector has a big pool of programs to move deeper into clinical development in the coming years. And money has flooded into the industry to fund these programs.
Tailoring supply chains to challenging modalities
The ongoing rise of advanced therapies is forcing the industry to rethink clinical drug distribution. In general, advanced therapies are more sensitive to environmental factors and face a tougher, more time-pressured set of logistical challenges than other modalities.
For example, production of autologous cell therapies, such as anti-cancer CAR-T treatments, entails taking cells from a patient, shipping them to a remote facility for processing and finally returning them to the trial site for administration back into the same patient. The faster this process happens, the sooner the patient begins receiving the potentially life-saving treatment.\
This makes supply chain mistakes potentially devastating for patients and highly costly for clinical trial sponsors. Analysts estimate that manufacturing of approved CAR-T treatments can cost $200,000 per dose.
The fate of millions of patients and billions of dollars therefore rests on the biopharma industry’s ability to master the complex supply chains that underpin the development of advanced therapies. The nascent nature of advanced therapeutics and the challenges they pose mean few supply chain service providers have a track record of managing these logistically-complex clinical trials.
Marken, a wholly owned subsidiary of UPS, is one of the companies with such a track record. In one example, Marken managed the supply chain for a Phase III trial of an active cellular immunotherapy. Production of the autologous therapy entailed shipping cells from patients at multiple study centers to a manufacturing facility in 24 hours. Delays and temperature excursions rendered cells unusable.
To manage and optimize the supply chain, Marken did a lane-by lane risk assessment, worked with the client to create a chain of custody document and timed collections to ensure the manufacturing facility would be ready to process cells upon arrival. Marken originally provided conditioned Credo boxes for 2 to 8°C shipping, and prepared 15 to 25°C boxes when the protocol changed mid-study.
On another occasion, Marken procured ready-to-use cryogenic shippers to support a Phase 2 trial that needed to transport a drug to investigator sites at -80ºC. As cryogenic shipper rental companies are regional and generally do not work 24/7, Marken sourced suitable facilities around the globe and managed the supply chain from its Global Control Center.
In both cases, Marken used technologies to track shipments from sites to the production plants and back again, thereby making the process transparent to the clients and showing that the supply chains consistently complied with the protocols.
Using scale to provide flexibility and control
The case studies are illustrative of recent changes to development pipelines and the pressures they have placed on clinical drug distribution. These trends will continue to advance in the years to come, making it ever-more important for vendors to provide transparent, closely-controlled global supply chains. In light of these trends, Marken is striving to reduce its use of commercial aircraft.
Through its parent company UPS, Marken has access to an expansive airline network that can carry shipments. This enables Marken to manage the entire process via a hybrid solution. Shipments are collected by Marken, put on flights run by UPS and then carried to their final destination by Marken.
The hybrid solution, which covers Europe and the Americas, gives Marken end-to-end oversight and lessens time pressures. In Brazil, the introduction of the service extended the latest pickup times for 21 cities by up to 5 hours, giving investigators more time to prepare and package samples.
Hybrid supply chains are furthering the move toward personalized logistics. Between Marken and UPS, there is a near-endless number of possible combinations of supply chain resources, making it practical to tailor the solution to the unique needs of each clinical trial, the patients enrolled and the protocol.
This flexibility means that as the ongoing evolution of clinical-phase pipelines forces drug distribution to adapt, Marken will have the toolkit to create new supply chain solutions tailored to the changing needs of the industry.
1. Pharma R&D Annual Review 2018. Available at: https://pharmaintelligence.informa.com/resources/product-content/sitecore/shell//~/media/informa-shop-window/pharma/files/pdfs/pharma-rd-annual-review-webinar-2018-slides.pdf. (Accessed: 14th January 2019)
2. 2019 State of the Industry Briefing. Alliance for Regenerative Medicine Available at: https://alliancerm.org/wp-content/uploads/2019/01/State-of-the-Industry-2019-FINAL.pdf. (Accessed: 28th January 2019)
3. Annual Data Report 2015. Alliance for Regenerative Medicine Available at: https://alliancerm.org/wp-content/uploads/2018/04/ARM_Annual_Report_2015_Web_Version_FINAL.pdf. (Accessed: 28th January 2019)Back to Index