Overcoming the Challenges and Complexities of the Personalized Medicine Supply Chain

The last decade has seen an increased emphasis on research and development into personalized medicines, including cell, gene and immunotherapy treatments

A trend that is expected to continue due to the forecasted 8.74% CAGR of the personalized medicine,targeted therapeutics, and companion diagnostics market to $149 billion by 2020.These lofty expectations are due in large part to advancements in science and the availability of more sophisticated diagnostic tools, which are giving the medical community a better understanding of the human genome and make it easier to detect genetic mutations effecting an individual patient.

Specifically, 2016 witnessed the rst ex-vivo stem cell gene therapy to be approved by the European Commission to treat patients with the rare disease ADA-SCID (Severe Combined Immuno deficiency due to Adenosine Deaminase deficiency).Martin Andrews, Head of the Rare Disease Unit at GlaxoSmithKline,calls the successful approval of Strimvelis “the start of a new chapter in the treatment of rare and genetic diseases.”

If Strimvelis truly delivers upon its initial success, it could signal a disruptive new phase in medicine, where a one time gene fix or treatment replaces a life long dependence on taking a medicine and continuous treatment. Already, several hundred gene therapies are in development with the hope of providing a true cure for one of the 5,000 rare diseases caused by the error in a single gene.

The high potential that personalized medicines, including gene and cell therapies, have demonstrated for curing various types of cancers has led to a significant increase in the investment into these treatments, at both the institutional and industry level. According to intelligence firm Informa, the total financing in gene and cell therapy companies in 2015 came to US$10.8B, which represented a 106% increase over 2014. While institutional investment into cell and gene therapies is both necessary and significant, having the knowledge and understanding of the new technologies,represented by industry and corporate investment, gives this developing technology platform validity.

Therefore, the increase in corporate investment from US$58.9M in 2013 to US$2.432B in 2015, a colossal 4000+% jump over a two-year period, demonstrates a belief from large pharma that cell, gene, and immunotherapies can deliver upon their early promise. This has recently been demonstrated in the numerous corporate partnerships and acquisitions within the cell and gene therapy space. Which include Celgene’s recent US$1 billion investment in a ten-year collaboration with Juno, Amgen’s and Kite’s combined US$1.1B collaboration to advance CAR-T therapies , and Pzer’s desire to become the leader in gene therapy through their acquisition of Bamboo Therapeutics, Inc. for US$150M in August 2016.

The Personalized Medicine Supply Chain: Maintaining Viability and Safety 
While healthcare logistics is complex for all types of medical shipments – gene, cell and immunotherapy medicines present their own special challenges. It begins at the medical facility where a patient’s blood, plasma, white blood cells, tissue or tumor samples are harvested, during the process of apheresis, leukapheresis, or a biopsy. Samples are then transported to a Contract Development and Manufacturing Organization (CDMO) or processing facility where the personalized medicine is created for a specific patient. Once the cell, gene, or immunotherapy is prepared, it is returned to the medical facility or patient infusion site for administration.

To ensure adherence to the strict regulations of the life science industry, to maintain the integrity of a therapy in transit, and the overall safety of a patient, the supply chain solution developed for both the clinical development and commercialization of a personalized medicine must take the following into consideration:

• Time and Temperature Sensitivity
• A Strict and Transparent Chain of Custody
• Connectivity and Communication Between All Stakeholders
• Regulatory Compliance
• Scalability to Support Commercial Growth

Time and Temperature Sensitivity 
Since they can involve the transport of either cryo frozen or living cells, CAR-T and immunotherapy trial logistics are highly temperature and time sensitive. For one thing, multiple temperature profiles can exist for within one trial, with temperature requirements ranging from -196°, -80°, -20°, 2-8°, to 15-25° Celsius.

That means any supply chain solution must be flexible enough to accommodate different temperature requirements to and from the site, CDMO, or lab.Time is always an issue where clinical trials logistics are concerned, however, many of the personalized medicines currently under development have shortened stability timelines of 6 to 48 hours, which requires their transport and processing, or administration to occur within a highly abbreviated time frame. To ensure that these cell, gene and immunotherapy shipments arrive on time and within the correct temperature, careful pre-planning must take place. This includes:

• The pre-qualification of transport routes for every mode of transportation (air and ground)
• The procurement and conditioning of specialized packaging, such as Credos or Liquid Nitrogen Dry Shippers (LN2) for expedited placement at the hospital or CDMO
• The arrangement of in-transit storage based on Good Distribution Practices (GDP) principles and other best practices, including access to temperature controlled vehicles
• The establishment of detailed contingency plans to be able to proactively respond to and overcome potential transportation interruptions, such as weather, natural disasters, etc.
• The usage of technological advancements, such as GPS devices that provide real-time location data, as well as temperature, tilt, and other relevant shipment metrics.

Chain of Custody
In addition to the end-to-end safe transport between medical facilities, hospitals and CDMOs within product specifications, it is critical to the best patient outcomes that each therapy is collected from and delivered to the correct patient, pre- and post manufacturing.

This involves using sophisticated technology, such as QuickSTAT’s proprietary IT system QuickTRAC, to track shipments down to the specific patient ID number, from the point of pick-up through to delivery. In addition, it is critical to leverage the use of cellular-based GPS tracking devices with multi-sensory capabilities, such as real-time location, tilt, and temperature monitoring throughout the entire predetermined best transit route.

This results in complete control and visibility into the status of each shipment milestone and ensures the strictest chain of custody, from collection to customs clearance,and final delivery to a specific end user.

Communication and Connectivity Between All Stakeholders – Robust System & Experienced Team 
The transparency needed to link the hospitals, CDMOs, doctors, and patients within a personalized medicine supply chain requires seamless connectivity and communication between all of the previously mentioned parties.

QuickSTAT has been able to successfully support cell, gene, and immunotherapy supply chains, by leveraging our proprietary, built for purpose IT system, QuickTRAC. QuickTRAC was designed to integrate across all electronic platforms, allowing for real-time updates to all stakeholders regarding every milestone a shipment will encounter in route to delivery. By utilizing this technology’s ability to set alarms and alerts based upon pre-defined rules, QuickTRAC is able to send instant email notifications and updates to the relevant stakeholders regarding events that may impact a delivery deadline, including realtime geographic and temperature data. By receiving automatic real-time shipment alerts and constant oversight from an experienced logistics team to re-route shipments requiring alternative routing, the CDMOs are able to better schedule their manufacturing processes and the sites are able to better support the administration of a therapy to a patient.

Regulatory Compliance 
Due to the complexity of ever changing regulations that vary from country-to-country for various types of patient samples and medications, it is critical to engage an experienced and knowledgeable courier, at both the clinical and commercial planning stages, to review the import/export requirements of your therapy, as well as VAT, duties and tax considerations for all of the countries involved in a program. By having an experienced team to guide you through the regulatory and customs requirements for the transport of your personalized medicine, a strong logistics plan can be developed to set up robust standard operating procedures to govern your global supply chain throughout the therapies clinical development and commercialization.

Scalability for Commercial Growth 
With the commercialization of a trial or drug product comes a substantial increase of patients, sites and manufacturing facilities – leading to an exponential growth in expected shipment volumes. Supply chain capabilities must be available to immediately manage the growing demands resulting from the varied time and transit specifications needed to accommodate an expanding geographical coverage.

Specifically, commercialization requires end-to-end turnkey capabilities for personnel and customer service, a robust global distribution network, packaging that allows for universal conditioning procedures across differing climates, a robust IT infrastructure that can automate much of the supply chain’s QuickTRAC was designed to integrate across all electronic platforms, allowing for real-time updates to all stakeholders regarding every milestone a shipment will encounter in route to delivery.

communication, demonstrated contingency plans with cost effective redundancies, an in-depth understanding of regulatory and customs requirements, and seamless  connectivity to all stakeholders involved. By taking all of these factors into consideration, it will also help a sponsor to determine a critical piece of its commercialization strategy, namely the best location for a manufacturing partner of the therapy from both a logistics and cost standpoint. As our industry continues to invest in the development of cell, gene, immunotherapies and other personalized medicines, it is crucial that sponsors leverage the experienced personnel, state of the art IT systems, and global infrastructure of a global supply chain provider early on in the planning process. The best specialist logistics providers will maximize their knowledge, experience, and technology to serve as the critical communication bridge and supply chain network between the sites, CDMOs, doctors, and patients that is necessary to deliver successful clinical and commercial outcomes.