Two of our experts with deep experience in Agile Commercial Launch answer six insightful questions on how applying Agile launch techniques can help get life-saving treatments to patients faster.
Bring Precision Medicine To Market
Diverse Therapies Creating Complexity
We live in an amazing time when it comes to biopharmaceutical drug discovery and development. The FDA has approved innovative medicines with differing approaches, platforms, technologies, and modalities. As we leverage new technologies, our strategies for drug discovery are leading to therapeutic diversity which is rapidly becoming a complicated landscape for manufacturing teams.
Figure 1. The Accelerating Pace of Innovation in the BioPharma Industry is Creating Tremendous Diversity and Complexity for the Manufacturing Organization
With modalities as diverse as small molecules, monoclonal antibodies, CAR-T cell therapies, RNA-based therapies, and personalized vaccines and medicines for patients, the portfolio strategy for Executive leadership and R&D teams has led to increasing complexity for Chief Manufacturing Officers and their teams.
| Novel Technologies & Platforms
Figure 2 shows a few recent examples of these product launches – almost all are first-in-class therapies solving real health problems with diverse modalities.
Figure 2. Recent FDA approvals have created complexity for manufacturing teams.
As these companies are acquired, leadership is discovering that the traditional paradigm ofacquiring, integrating, and closing the acquired organization is no longer feasible because they cannot easily replicate the expertise and manufacturing capabilities.
Car-T Cell Therapies
One of the most exciting new treatments coming to market is CAR-T cell therapy. This treatment utilizes reengineered T-cells tagged with a chimeric antigen receptor (CAR) to target patient’s cancer cells. As the Figure3describes,therearetwomethodsof CAR-T cell therapy, Autologous and Allogeneic.
Autologous therapy involves point to point infusion, taking cells from a sick patient, formulating them appropriately, then infusing back into the same patient. As you can imagine this requires supply chain intricacies to ensure that the one-to-one infusion is maintained. In addition, due to the long lead-time between collection and treatment as well as severity of disease progression in patients receiving CAR-T therapy, patients have passed before receiving their infusion.
Allogeneic therapy does not rely on point-to-point treatment but instead collects T-cells from healthy donors. Once cells are transduced with the viral vector (CAR) they can be inventoried for off the shelf infusion for many patients. While this simplifies the supply chain tracking and reduces the lead-time for treating a patient, Allogeneic therapies come with their own complexities. For example, identification of suitable donors that qualify for cell collection is incredibly difficult. Donors must not have been infected with a variety of different illnesses to ensure a consistent T-Cell is collected. In addition, there is high variation between donor cell yield during proliferation that is not yet fully understood.
Many of the raw materials and production facilities required for CAR-T therapy manufacturing stem from a small group of key suppliers (Lonza, Lentigen, WuXi, etc.). As the market continues to grow, these suppliers are forced to either expand their production capacities or selectively choose which customers will receive their goods/services. Of course, start-up demand is much smaller than that of a later stage company and without strategically partnering with big pharma companies that have “supplier pull” they may be considered second priority to suppliers. This leaves smaller biotech companies at a potential disadvantage. Figure 4 shows key suppliers across the supply chain.
Figure 4. Prominent suppliers in the CAR-T space.
While it is potentially possible to use multiple suppliers, variation in different supplier raw materials (and even production practices) raises additional regulatory questions that could impact approval and potentially require comparability studies to evaluate purity, functionality, and efficacy.
As the space continues to grow, invariably more suppliers and novel technologies will emerge. Companies of all sizes must keep a finger on the pulse of the supplier market, continuously vetting emerging raw materials, equipment, and manufacturers while balancing this with production longevity.
Next Generation Sequencing (NGS) and Application to Personalized Vaccines and Therapeutics
Sequencing technologies will further integrate into the manufacturing environment as we develop personalized medicines and vaccines for patients. With Sequencing technologies, this is fast becoming a reality. But these technologies require a clinical laboratory (CLIA -Figure 5) to do the sequencing, for the sequences to be sent to the manufacturing facility, and for that manufacturing facility to produce the personalized therapeutic for a patient.
Figure 5. Next generation sequencing’s end-to-end solutions.
Sequencing businesses focus on end-to-end workflow solutions that allow informed decision-making by Doctors and Patients.
Sequencing businesses will support pharmaceutical and biotech companies that want to produce customized vaccines and therapies for Patients.
For the Chief Manufacturing Officer and their teams, this means integrating production processes with sequencing technologies along with CLIA labs (Figure6) to analyze and provide instructions for customized therapies to the manufacturing plant’s teams.
Figure 6. Operations for personalized therapies involving NGS technologies.
Personalized Therapies Require New Systems
The need to treat each patient as a unique scheduling, setup, processing and fulfillment challenge is requiring innovative supply chain concepts to manage chain of custody, keep bottleneck operations utilization rates high, while delivering effective and safe treatments. Currently these new challenges make treatments costly and provide significant opportunity to innovate and reduce costs in delivering personalized treatments.
In the more conventional treatments, target indications are addressed with specific molecules keeping the technical operations separated from the patient in meaningful ways (Figure 7) and are typically focused on finished goods inventory levels. Today’s “every patient is a batch” more intimately links treatments with patients and as such requires new controls on work in process inventories and finished goods (Figure8).
These new controls often take the form of new digital and physical systems (Figure 9). Because the patient is linked to tech-ops in this environment, the digital assets (software technology to schedule, track, and administer medicines) may also be a required part of the BLA Filing.
| What Is Needed To Scale For Success?
Partnerships, Acquisitions, or Unicorns
There are different strategies and business models a company can use to have R&D and Commercial success. Those pathways differ for each company and there are many options. In general, companies that raise capital smartly, invest wisely, and strike key partnerships with great science are the most successful.
Companies have followed different strategies, and history shows us that certain paths are less risky for longer-term success for the startup organization. Strategies have included Partnership, Acquisition, and Unicorn.
There are many examples of companies (Figure 10) with a primary strategy of raising money, sharing risks and costs, and having expertise to development and launch a successful first drug candidate through a “Partnership Strategy.”
Figure 10. Examples of successful partnership strategies… with an acquisition finale
There are far fewer examples of “Unicorn Strategy” companies (or as close as you can be) prior to launch of their products (Figure 11).
Figure 11. Examples of successful unicorns and their products.
Each company must assess their assets, the pros and cons of each strategy, and the best path forward for their company and patients. In the end, any company’s strategy must translate into shareholder value. The investments they make and choosealongthewaycanhaveafavorableornegativeimpactontheirbusiness. Scimitar conducted a benchmark on companies by stage of development comparing investments in staff size, R&D, SG&A, and in their programs (Figure 12).
Figure 12. Comparing investment strategies across the development lifecycle.
Staff: Managed transitions and hired the right people at the right time.
Portfolio Balance: Had one Phase 3 program, one Phase 2 program.
Partnerships: Had one or two large pharma development partners to support development costs and diversify risk.
As with the emergence of MAbs30+ years ago, companies had to determine how best to manage small molecule and biologics. Organizations created central teams with capabilities such as Quality Assurance, Demand Planning, and CMC Regulatory to manage a portfolio of products with differing modalities. In other cases, companies deployed highly specialized resources to ensure the right technical capabilities such as MSAT, Supply Chain, and Quality Control. The solution at each company will be different, and will depend on their unique circumstances, with the common goal of providing patients with the highest Quality while managing cost and budget implications.
Network Strategy: To Build, Partner, or Both
This will all depend on the company’s stage of development and commercialization. There is tremendous competition for resources –in many cases CAR-T Cell companies and gene therapy companies are competing for several of the same contract manufacturing organizations (CMOs), suppliers, and contract testing labs (CTLs). Supplier consolidation has created an environment of supplier power, and weaker positions for the biopharmaceutical manufacturing teams to negotiate effectively, potentially leading to higher costs in the future. As a result, a strategy that solely uses CMOs will not be sustainable in the long-term, and companies will need to evaluate in-house manufacturing capabilities.
Strategies for Harnessing the Power of the Immune System and Genome
As companies acquire more diverse assets aligned with their strategies, companies face the dilemma of modality diversity creating complexity (see Figure 13).
Figure 13. Companies are looking to Bolster, Treat and Alter immune systems to stop diseases.
Scimitar Inc. is positioned to help clients with experiences across the spectrum of modalities and across all functional areas of the value chain. With the goals of immediate impact and long‐term company success, Scimitar supports clients in their goal to help patients live better lives.
| Case Study 1
A $3.5B CAR-T Cell Therapy Startup Experiencing Rapid Growth and Required a Supply Chain Assessment
Partnering with the client, the Scimitar Inc. team:
- Initiated a cross-functional core team consisting of members from supply chain, product development, and QC
- Held several working team sessions to assess risk across the organization
- Assessed both quantitative and qualitative risks, translating tribal knowledge into measurable metrics
The Scimitar Inc. team worked collaboratively across the organization to build an end-to-end supply chain materials map including key equipment and QC testing.
- Executed a cross departmental evaluation of all key raw materials
- Developed mitigation plans, priority, and business cases for raw material specific risks and for risks across the supply chain
| Case Study 2
Newly acquired CAR-T Cell Therapy Company established growth targets required aggressive scaling of lab, infrastructure, and operating systems.
- Diverse cultures working within rapidly changing operational environment
- Several IT systems integrated with the Cell Therapy offering
Assessment and IT Integration Planning for support of growth targets and reduction of complexity of key operating systems.
Scimitar Inc. delivered assessment and transition risk mitigation plans including:
- Approved Hybrid Resource Model Site IT Leadership Transition Plans key system risk areas and mitigations plans
- Mitigation levels and timing
| Case Study 3
A late-clinical stage CAR-T cell therapy company needed a flexible 5-year manufacturing network strategy to manage operational costs and risks, as demand transitions from clinical to commercial.
- Assessment of supply network options, their risks and costs
- Modeling of options to estimate capacity needed to meet service levels
- Cost estimation of recommended supply network strategy
Scimitar Inc. delivered a 5-year supply network strategy, including:
- Available options for increasing capacity
- Optimized plan to time capacity expansion
- Capex planning to balance capacity and risk
| About The Author
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Scimitar is a global management consulting firm that provides life science companies with clear, actionable, and data-driven strategies on growth, profit improvement and M&A.
We move beyond strategy and help to implement and deliver the value we promise.
Find out more: www.scimitar.com
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