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Cell & Gene Therapy Insights

Cell & Gene Therapy Insights

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Spotlight Article

Commercial Lessons for Clinical Success

Strategies for Scale-up & Scale-out

Simon Ellison, Heidi Hagen and Christophe Suchet

Advanced therapies require highly-sophisticated advance planning. For long-term success, transformative cell and gene therapies rely on a risk-based understanding of the supply chain, with all aspects mapped out early. Recent draft guidance from regulatory authorities stresses early end-to-end systems thinking and data management capabilities. A commercially-minded approach to each clinical phase will help create viable commercial supply chains and patient journeys from the beginning. This article provides valuable commercial-phase insights from industry veterans with deep commercialization experience, and discusses how these lessons can be applied to clinical-phase therapies to help drive advancement and success.

DOI: 10.18609/cgti.2018.107
Citation: Cell Gene Therapy Insights 2018; 4(11), 1131-1138.
Open access

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In the offices of an early-stage biopharmaceutical developer, the team has received exciting news. Their early-phase advanced therapy trial, currently operating at just one clinical site, has earned investigators’ interest and will expand faster than planned.

The Chief Medical Officer hopes to expand the trial to four clinical sites within 10 weeks. The initial site, located in a major city with two airports, runs smoothly. Leukapheresis takes place in the morning, allowing for rapid transfer of collected patient material to a nearby airport within hours. The clinical site is geographically close to the manufacturing site, meaning that the patients’ cells are shipped to manufacturing overnight. Traceability and logistics have been run manually. Three patients have been treated, with a fourth patient journey in process.
This initial success raises the team’s optimism as they consider the new clinical sites —two based in major metropolitan areas much farther away, and a third in a more rural location with one smaller, remote airport. There, leukapheresis will be performed at a local blood bank, not at the clinical site.

The therapy continues to change patients’ lives. But as the trial tries to grow, operations falter, and the therapy never reaches patients at commercial scale. Why?

The company had secured funding, trained clinicians, and managed costs. But as the trial grew, its operators did not account for the complexity that scale brings. Moving therapies through multiple airports, time zones, hospital systems—plus the tracking challenges that emerged—became daunting. An efficacious and safe therapy couldn’t reach more patients because the company had not understood the criticality of building a digitally scalable, traceable logistics platform.


Critical lesson: start with the end state in mind

For long-term success, advanced therapies require a risk-based understanding of the supply chain with all aspects mapped early. Recent draft guidance from the U.S Food and Drug Administration on the use of expansion cohorts in first-in-human clinical trials for oncology drugs and biologics stresses early end-to-end systems thinking and data management capabilities. The draft guidance states [1]:

“To… protect patients, it is imperative that sponsors establish an infrastructure to streamline trial logistics, facilitate data collection and incorporate plans to rapidly assess emerging data in real time and to disseminate interim results to investigators, institutional review boards (IRBs), and regulators.”

As three pioneering leaders in advanced therapy operations and delivery, we present commercially-minded thinking on the use of clinical phases to create viable commercial supply chains and patient journeys from the beginning. While these lessons apply to a wide variety of advanced therapy indications, this article will focus most directly on oncology, currently the largest single indication being pursued [2].


Development phases in Advanced Therapies

As part of a commercially-minded approach, it is also important to note that in biopharmaceutical development, the nature of clinical phases is changing. In advanced therapies, that change is accelerated. Increasingly, clinical phasing doesn’t conform neatly to the norms of “Phase I,” “Phase II,” “Phase III,” and “Commercial Launch.” We’ve often seen five phases emerge, rather than the traditional four, with some activities pulled forward earlier and new activities emerging. In this section, we outline our view of these five phases, with success factors for each.


Concluding insights

Advanced therapies face a pivotal moment. With more than 570 [7] oncology-focused advanced therapies in the discovery pipeline, now is the time for early-phase developers to benefit from lessons that accelerate patient journeys.

Here are final take-aways:

  • Understand the evolving nature of each development phase in advanced therapies. First-in-human trial designs and expedited designations such as the EMEAs PRIME or FDA’s RMAT or Breakthrough Therapy designations present the opportunity for accelerated trial processes and may require logistics and systems thinking earlier than anticipated. The Phase II+ “Operate” period is critical, laying essential groundwork for the logistics platform, COI/COC and COCn at scale.
  • Commercial success brings more innovation. A successful therapy developer may face the need to manage a commercial therapy and a pipeline of emerging clinical-phase products all at the time. Try to standardize underlying systems across all products as much as possible. While it’s common to use different systems for commercial and clinical, this bifurcation may reduce efficiency, increase costs, and introduce increased risk.
  • The advanced therapies industry is increasingly comfortable with clinical and process development stages. But logistics and traceability are just as important and can have significant effects on product development and future commercialization. Consider a risk-based approach to understanding your critical logistics attributes. Aligning your logistics platform development and your clinical and manufacturing platforms will save time and cost, as well as support a more efficient transition to commercial scale.

Above all, seek input from industry experts who have been there before. Partners who you might typically call “vendors” are actually technical experts who have overcome the challenges you face. A large number of learnings already exist in this nascent industry. Working with the right partners to plan out development, scale logistics, and properly time e-systems, automation, and integrations will be a critical factor on the journey to commercial success.

Figure 1. Advanced therapy clinical journey: the patient is the process and the product.

 

Figure 2. Clinical Phases for Cell and Gene Therapies.
* Including PRIME, RMAT, Priority Medicines Eligibility, Breakthrough Therapy Designation
1) Approved for testing in humans 2) Drug approved.

 

Figure 3. Building a logistics platform. Logistics Platforms are essential to enable the seamless flow of advanced therapies through their supply chains. Logistics vendors are technical experts who should be partnering with therapy developers in developing their assets through clinical trials into commercial operations.  To do this, they need to utilise their in-house skills (blue section) but also build links with other critical parts of the supply chain (magenta section).  This integration, in advance of therapy developers’ individual needs, creates strong supply chains and supports the development of robust, therapy specific Logistics Platforms that can operate at clinical and commercial scale.


Financial & competing interests disclosure

The authors are senior leaders at Vineti Inc and World Courier. No writing assistance was utilized in the production of this manuscript.


REFERENCES

1. U.S. Food and Drug Administration, Expansion Cohorts: Use in First-In-Human Clinical Trials to Expedite Development of Oncology Drugs and Biologics Guidance for Industry, August 2018. https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM616325.pdf

2. Alliance for Regenerative Medicine, Quarterly Data Report, November 1, 2018. http://alliancerm.org/wp-content/uploads/2018/10/ARM_Q3_2018_Web-1.pdf

3. U.S. Food and Drug Administration, August 2018. https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM616325.pdf

4. U.S. Food and Drug Administration, August 2018.

5. U.S Food and Drug Administration, Regenerative Medicine Advanced Therapy Designation, February 2018.
https://www.fda.gov/biologicsbloodvaccines/cellulargenetherapyproducts/ucm537670.htm

6. U.S. Food and Drug Administration, August 2018.

7. Alliance for Regenerative Medicine, November 2018.


Authors

HEIDI HAGEN, CHIEF STRATEGY OFFICER AND CO-FOUNDER, VINETI INC. Heidi has been an Operations Executive in the Biotechnology industry for over 25 years and is a Co-founder of Vineti. She has an extensive and proven track record in leading operations and commercializing innovative technologies ranging from recombinant protein/device combinations to the first active immune cell therapy, Provenge. Previously, Heidi was the Global COO for SOTIO, in Prague, Czech Republic with a US office in Boston, MA. Before joining SOTIO she worked for Dendreon for ten years as Senior Vice President of Operations and ten years with Immunex Corporation in a range of roles in drug development and operations management. Heidi has a B.S. in Cell and Molecular Biology, an MS in Bioengineering, and an MBA from the University of Washington.

CHRISTOPHE SUCHET, CHIEF PRODUCT OFFICER, VINETI INC. Christophe brings more than 20 years of information technology and senior biopharmaceutical IT experience to Vineti. Most recently, he served as Vice President of IT for Kite Pharma, Inc., where he developed the essential technology systems that helped Kite’s first cell therapy receive FDA approval, scale rapidly, and secure the landmark sale of the business to Gilead Sciences, Inc. Prior to Kite Pharma, Christophe served as Vice President of IT at Pharmacyclics Inc., a clinical stage and commercial biopharmaceutical company that grew in two years from no product revenue, to $1 billion revenue, to acquisition by AbbVie for $21 billion. Christophe has served as Genentech’s Director, IT Pharma Development Applications, and as IT Director, SAP Center of Excellence & Enterprise Applications. He received his M.S. in Biology and Economy from AgroParisTech.

SIMON ELLISON, CELL AND GENE THERAPY SERVICE DIRECTOR, WORLD COURIER. Simon is the Cell and Gene Therapy Service Director at World Courier.  His role is to develop a logistics platform that supports the growth of the advanced therapy industry through clinical development and into commercial operations. Whilst at the Cell and Gene Therapy Catapult he identified the need for, and built the Seamless Freight portfolio. He also helped develop the commercial operating model for the Catapult Manufacturing Centre that resulted in the first collaborators entering, and the start of a cluster forming around this unique facility. Prior to this, Simon was the Head of Commercial at NHS Blood and Transplant (NHSBT) where he merged the needs of the industry with NHSBTs manufacturing and supply chain capability. This enabled multiple UK and international organizations to move their therapies forwards.

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