Deloitte’s Omkar Kawalekar, Hussain Mooraj, and Amit Agarwal examine the evolution and future of cell and gene therapy manufacturing and the areas in which biopharma firms need to invest in order to succeed in this emergent field.
Cell and gene therapies (CGT) are the next evolution of personalized health care. These products are potentially curative in nature, highly tailored for specific disease indications/individual patients, and have shown promising efficacy in disrupting existing therapy paradigms.
Working closely with CGT companies over many years, we have learned that a crucial component of CGT’s success is reliable, consistent, and scalable manufacturing—something that continues to be complex and challenging. Our clients have discussed challenges such as reliable raw materials supply, end product yield, consistent quality, scalable manufacturing, and value chain complexity. While the problems are well-understood by market players the solutions have been harder to come by. Here, we shed light on a few concepts that can help redefine how we should think about CGT manufacturing.
Investing in sufficient and reliable manufacturing capabilities is vital to successful CGT production and launch. We have seen companies making large capital investments—sometimes up to $500 million—to build their own manufacturing facilities. We also have seen companies at the opposite end of the spectrum. Some organizations continue to invest in partnerships with external contract manufacturing organizations (CMOs) and spending almost as much in leasing suites for long-term capacity, even if they are not being used. This has placed a massive capacity constraint on the supply of GMP-grade materials (sometimes leading to a 12-15-month wait time for the supply of critical CGT materials, such as viral vectors). In our conversations with several CGT company senior executives, they expressed regret for not investing in sufficient manufacturing capacity years ago. Having control of your own CGT manufacturing capacity has become one of the biggest rate-limiting steps in being able to launch and grow revenues. Therefore, CGT companies small and large should re-evaluate their manufacturing strategies and plan future investments accordingly.
CGT organizations are exploring new ways to build and control manufacturing network capacity at more affordable costs. We have observed the emergence of risk- and space-sharing models to spearhead innovation from modestly funded start-ups by increasing capital investment efficiency, lowering risks, and shortening time to market. One such example is ElevateBio, which has built a centralized facility and supporting capabilities including highly skilled talent, manufacturing infrastructure, and processes to provide CGT companies a commercialization launchpad. Such models are financially attractive to companies that do not have the capital to build their own manufacturing facilities. An alternative approach is to decide which part of the value chain companies should build versus buy. Several CGT clients have decided to outsource/partner for the final drug product manufacturing while investing in manufacturing capacity for the critical raw materials (e.g., viral vectors). This type of configuration allows the company to lessen the risk of single product failures in the clinic because the raw materials can be used in multiple portfolio products.
Many big pharma companies struggle to position new CGT offerings within traditional monolithic operational models, which favor supply chains built around products, are push-based, and are heavily reliant on inventory. CGT manufacturing—especially individualized therapies—requires a clinically connected value chain that is built around patients, highly agile, and usually pull-based. We see multiple models emerging, including establishing standalone business units, absorbing CGT in therapeutic franchises, or a blend of the two. Leading organizations in this space have assembled cross-functional teams to design operating models centered around patient and clinical staff pain points. The aim is to create a highly matrixed organization that is supported by a flexible, integrated technology infrastructure that can help standardize processes for certain capabilities and build product-specific processes for others. Companies cannot ignore the necessities of today; however, they should consider developing bi-modal operating models to accommodate the CGT value chains of tomorrow.
Invest early in your manufacturing strategy. Take into consideration the level of upfront investments you want to make versus your risk appetite for capacity constraints. If cash-strapped, consider the option of building your own pilot manufacturing facilities to support early-phase clinical investigation for multiple CGT assets and perfect your processes. Identify leading candidates early and then negotiate with manufacturing partners for successful advancement.
Design your value chain to win. There is no one-size-fits-all CGT operating model. Design your value chain from an outside-in, patient-oriented perspective. The enabling digital core and its components (systems, databases, and tools) should provide end-to-end value chain visibility and an opportunity for broad interconnectivity.
Embrace risks and push the envelope. Even in today’s uncertain times, human nature drives us to find opportunities in crisis. Embrace risks and invest in future-focused technology, such as fully automated/robotic manufacturing modules, to prepare for continued unpredictability, spur innovation, and deploy CGT to patients in need. Erbi Biosystems, Invetech, and MultiplyLabs, for example, are developing cutting-edge robotic systems for industrial-scale manufacturing.
 “Pfizer Invests $500 Million in Gene Therapy Manufacturing Plant,” Bloomberg.com, August 21, 2019, https://www.bloomberg.com/news/articles/2019-08-21/pfizer-invests-500-million-in-gene-therapy-manufacturing-plant
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