Life sciences companies supplying individualized cell and gene therapies (CGTs) will need to create digital capabilities that orbit around the patient and clinical service providers to achieve market uptake and product sustainability.
Cell and Gene Therapies (CGTs) are a nascent yet burgeoning element in the evolution of therapeutic technology (Figure 1). With more than 900 firms globally focused on these advanced therapies and over 1,000 cell and/or gene therapy clinical trials currently underway, the industry could see a tsunami of approvals - as many as 10 to 20 new therapies per year - starting in 2025.1 This wave of CGT development and deployment is compounded by pharmaceutical companies’ growing spending to include more CGT offerings in their drug portfolios. In 2018, investors committed over US$13 billion globally to advanced therapies, including cell, gene, and gene-modified cell therapy. In 2019, nineteen CGT-related M&A deals worth over US$156 billion were completed.2 CGTs are becoming a staple of biopharma’s menu; however, simply offering these lifesaving therapies is not enough.
Compared to chemical-based pharmaceuticals, CGTs depend more on clinical institutions and hospital networks to facilitate drug administration to yield the most effective results (and, in some circumstances, any results at all). Because of this, CGT-supplying organizations and, notably, pharmaceutical parent companies, may need to adapt historical processes, roles, and value chain organizational structures to be able to deliver their product and successfully collaborate with point-of-care (POC) providers. This article discusses the need for life sciences companies to create new digital capabilities that accommodate CGTs’ - specifically autologous, ex-vivo therapies - unique requirements, manage unavoidable exception scenarios, and build potential differentiators in their digital offerings. We also assess the prospects of an industry utility and a logical systems architecture to maximize the returns on companies’ IT investments.
New System Requirements for Most CGT Products
CGT advances are accelerating the convergence of pharmaceutical companies and POC providers. For more advanced CGTs, the definition of a treatment center versus a pharmaceutical company gets blurry as personalized therapies become localized/regionalized around the treatment center. Autologous, ex-vivo CGT suppliers have to plan their manufacturing around patient inputs; the patient’s cells being extracted and delivered to the manufacturing site is a physical constraint that all ecosystem participants have to navigate and accommodate. As such, traditional demand and capacity planning models do not map cleanly to CGT product manufacturing processes. Manufacturing according to schedule means that the patient has promptly provided cells on the initial treatment timeline, which frequently is not the case. Additionally, the concept of track and trace (referred to as Chain of Identity [COI] and Chain of Custody [COC]) is absolutely critical to ensure that the intended patient receives the right drug product. This requires an unprecedented degree of tracking the biological product from start to finish (COI), while also continuously recording each change of the product’s ownership (COC).
Thus, a CGT manufacturing organization (whether a contractor or vertically integrated within a CGT manufacturer) needs to conceive upstream processes to handle material quality and timing at a greater degree of variance than in traditional manufacturing. Specifically, operations likely need to shift from using inventory to de-risk supply to providing a just-in-time (JIT) value chain with varying and hard-to define material input, delivery, and service windows (Figure 2).
Developing Clinically Connected and Digitally Enabled CGT Processes
If CGT manufacturing and/or therapy delivery are prohibitively difficult, elongated, or expensive, patients likely will not benefit even if drug discoveries and approvals continue. Thus, it is vital that CGT suppliers build a value chain around the patient that is both clinically connected and digitally enabled. The benchmark is to design these processes and capabilities to best harmonize with clinical service providers and the patient. As one CGT executive put it, “We’re building the plane as we’re flying it.”
Given the intersection between CGT suppliers and clinical service providers, roles that accurately represent POC needs are recommended staples of a CGT resource mix. A resulting example of a new subfunction that depicts this role is patient operations, team members that operate at the delicate intersection of manufacturing process, treatment site, and patient.
CGT manufacturers should seek and use a broad swath of input from various functions so that gaps in the external treatment lifecycle experience can be identified and closed, potentially using new digital offerings that support:
- Treatment timeline visibility: Knowing when the POC will receive the finished product back at the infusion site so they can coordinate with the patient, or search for alternative treatment options that can return a viable product sooner.
- Treatment updates: Receiving key updates throughout the treatment lifecycle so that intermediary steps can be taken with the patient to prepare them for eventual infusion, maximizing treatment efficacy.
- Notification preferences: Having the digital infrastructure to allow hospitals to receive more or fewer notifications, as desired.
- Role permissions: Having system-based role definitions (the ability to submit an order) versus function-based role definitions (nurse) to enable flexibility when setting up new treatment centers and users.
- Localized data capture: Being able to capture different treatment information from the POC based on geography and indication factors (e.g., capturing a Medical Record Number for a commercial order instead of a Treatment Protocol Subject ID for a clinical order); this also requires regulatory alignment.
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Building Differentiated Capabilities with Digital Investments
In addition to building and/or strengthening the above capabilities, leading CGT suppliers will look for ways to responsibly differentiate in four core areas that can drive value at POC:
- Ease integration with external partners. Build a platform that seamlessly integrates with other stakeholders’ systems, such as hospital EHRs, 3PL systems, and patient registries.
- Own the indication by leading in patient education. Enhance applications to become an education portal for patients and caregivers.
- Continuously improve process and outcomes. Run analytics on the longitudinal order/patient-specific data captured along the patient and cell journey to help inform operational performance as well as patient outcomes.
- Engage proactively with regulators on requirements. Use data-driven insights to engage with regulatory authorities early and help flex requirements (e.g., at the time of Biologics License Application [BLA] filing).
Forward-thinking CGTs will focus on features that make life easier for service providers and the respective hospital network. Efficiencies created over time in a phased approach, in conjunction with positive product outcomes, should drive competitive advantage and marketplace differentiation.
Managing Exceptions
Pairing POC stakeholders with Information Technology (IT) and other functions can help CGT suppliers unlock solutions (or process improvements) to handle common exceptions that arise in the CGT treatment lifecycle. Autologous ex-vivo therapies require physical material from a patient, creating variability in manufacturing raw material and manufacturing timing on an order-by-order-basis. Both factors have impacts across the treatment lifecycle and manifest themselves in common exception scenarios such as:
- Apheresis (pick up) rescheduling: According to anonymized large providers of CGTs, apheresis reschedules happen in 40 percent to 60 percent of all orders. The most frequent causes are patient availability or health condition, along with timely insurance approval. Systems supporting CGT scheduling must be able to accommodate these changes.
- Out-of-specification: It is a common manufacturing scenario to have outcomes that do not yield required cell counts for compliant doses, forcing the manufacturing run to terminate or go out-of-specification. Digital capabilities should handle these exception scenarios.
- Holding finished product inventory: In some cases, manufacturing for an order may be completed but the infusion location does not have the capacity to hold the finished material as planned. The ability to digitally pause order movement and treatment timelines should be embedded within these capabilities.
CGT suppliers require a robust process and digital capabilities to maintain manufacturing slots amid raw material arrival uncertainty. This process must also accommodate for off sets between variant pickup locations and manufacturing plants. Ideally, a CGT supplier will create a tollgate oriented around the apheresis center where order scheduling and capacity confirmation can occur.
To digitally manage out-of-specification orders, the CGT supplier should first consider the communication process back to the site, then align on the presentation of that manufacturing determination. From a cost perspective, creating the right system identifiers can drive an efficient re-valuation process for commercially out-of-specification orders.
For all processes, CGT firms should constantly pressure test systems against the unlikely, have an approach offline, or deviations to cover edge cases. The supplier must be able to deliver the most effective dose in an efficient manner.
Leveraging Industry Utilities
While differentiating digitally can drive value and improve the customer experience, it is important that CGT suppliers know where to differentiate versus standardize. Exceptions handling resiliency and nuanced POC requirements are two current digital differentiation rallying points, and others may be emerging.
Still, there are times when differentiation may be cumbersome. Leveraging industry utilities can enable development of standardized offerings to aid clinical service and POC providers. For example, the expected influx of new therapies - 10 to 20 new offerings per year starting in 20251 - has the potential to create disarray at POCs: If every CGT supplier is using a different portal for their products, bottlenecks will form for clinical service providers.
There currently is no aligned “portal provider” or single industry solution to be the face of CGTs at POC. Several existing products provide out-of-the-box functionality; these platforms compete with custom builds that are often more costly but have more flexibility to meet specific requirements. Figure 3 shows a representative CGT portal architecture that can operate as a consolidated point of entry.
Developing an industry-standard portal for pharma and POC providers may require guidance from a knowledgeable intermediary to bridge requirements and trade-offs. Deloitte’s Industry Working Group (IWG) was formed in collaboration with several CGT players to address areas where standardization is needed. The IWG brings together CGT industry experts, including top pharma executives, clinicians, apheresis nurses, quality assurance staff, and regulatory advisors, as well as technology solution company executives. The IWG discussed the topic of an industry utility at its most recent session (early 2020). The general consensus is to focus on patient outcomes and standardize shared aspects of CGT processes to lessen the burden on POC providers. Having a common landing portal shared across industry participants would be a considerable improvement over current disintermediated systems.
Labeling is another area where standardization is preferred over differentiation at POC. Labeling is an essential component of the apheresis and finished product processes, and a regulatory mandate for transporting blood products and maintaining chain of identity. To assist in achieving labeling standardization, Deloitte started the IWG Labeling Initiative. In close collaboration with the Standards Coordination Body, IWG prepared a proposal for standardizing the minimum required elements for labeling the apheresis product for autologous cell therapy manufacturing. These elements include label size, material, layout, and minimum data requirements, among others. Standardization will achieve efficiencies at POC by not having to consume or manage different labels across CGT suppliers.
Creating a Patient-Centric Architecture
If CGT suppliers are going to build a patient-centric, clinically connected value chain, they also should develop an enabling technology architecture. There currently is no one-size-fits-all solution for applications being leveraged across CGT processes such as ordering, scheduling, labeling, billing, and manufacturing. Creating a digital product that can facilitate a CGT treatment from beginning to end will require multiple applications to be integrated with specific lifecycle functions. The applications mix will likely include Manufacturing Execution Systems (MES), Customer Resource Management (CRM), templating software, treatment portals, middleware, and Enterprise Resource Planning (ERP) systems. When aligning the architecture to a CGT digital product, developers should:
- Consider a role-based architecture where end users can access only a subset of applications for greater operational efficiencies
- Determine where to leverage market and standard product applications where process and feature customization is limited
- Evaluate requirements for current and future releases and map them to potential fulfillment systems
- Limit integration calls across applications to reduce churn and Application Program Interface (API) chatter to create a more streamlined digital process
- Confirm native combinability for selected applications prior to design and build and select applications that have robust APIs to accommodate flexible scaling
- Assess digital roadmap capabilities against market products when evaluating a buy-versus-build approach
Outcomes Matter
Ultimately, CGT product uptake depends on the manufacturer successfully delivering at two fundamental “moments of truth”: (1) Was the product available and ready to be used on time and at the right location when the patient needed it, and (2) did the therapy bring about the outcomes that the physician and patient expected and desired?
CGT suppliers should challenge the process by asking:
- What levers can we push to deliver the product back to the patient faster while remaining in compliance?
- How can we accurately forecast a treatment timeline at the moment of order submission?
- What technical and procedural constraints are required to confirm logistics information is accurate on a transactional basis?
- Are there signals we can provide POC providers to increase product efficacy or patient readiness?
- Are there any internal processes we can compliantly adjust to increase product efficacy?
The CGT industry could greatly benefit from a digital solution that strives to addresses this set of questions while also ultimately enabling a positive answer to the two key moments of truth.
Endnotes
- Commissioner of Food and Drugs - Food and Drug Administration Scott Gottlieb M.D., “Evaluation and research on new policies to advance development of safe and effective cell and gene therapies,” US FDA, press release, January 15, 2019, https://www.fda.gov/news-events/press-announcements/statement-fda-commissioner-scott-gottlieb-mdand-peter-marks-md-phd-director-center-biologics.
- Deloitte analysis of M&A deals; data sourced via Thomson One Banker.
- Deloitte analysis based on CGT client discussions.
Author Biographies
Josh Fyffe, is a senior consultant in Deloitte Consulting LLP’s Customer and Marketing practice, focusing on life sciences and cell and gene therapies. In the last three years, Fyffe has worked closely with biopharma companies to define system capabilities and roadmaps for CGT products through scoping workshops, SME engagements, industry certification requirements, and global regulatory considerations. Josh maintains a detailed understanding of these requirements and processes to inform client-specific architectural and design considerations.
Omkar U. Kawalekar, PhD, is a manager in Deloitte Consulting LLP’s Strategy & Analytics practice and leads eminence for Deloitte’s NextGen Therapy practice. With a graduate degree in cell & gene therapy from the University of Pennsylvania, he has primarily worked with executives at small and large biotech companies, defining and implementing transformative capabilities as they develop, manufacture, and commercialize cell and gene therapies. He continues to present at numerous scientific conferences and publishes regularly in this field.
Hussain Mooraj is a principal and leads Deloitte Consulting LLP’s NextGen Therapy practice and is the New England regional lead for life sciences. He brings more than 25 years of experience in manufacturing, supply chain, enterprise technology, sales and marketing, and strategy consulting to his role. Mooraj works closely with senior executives from global life sciences firms, helping them transform their end-to-end businesses and build startup organizations to be able to launch lifesaving new therapies, especially on the CAR-T and gene therapy side.
Acknowledgements
The authors would like to thank Michael Cislo, Rajesh Singh, Jeffrey Lacey, and the many others who contributed their insights to this article.
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