In case you missed it, Invetech recently sponsored a webinar hosted by the International Society for Cellular Therapy (ISCT) focused on the key considerations for achieving commercial success for cell therapies.

The webinar featured presentations by Mike Paglia, senior director of technical operations at bluebird bio, who shared his insights on needle-to-needle logistics, as well as Mark Curtis, business development analyst at the Centre for Commercialization of Regenerative Medicine (CCRM), who discussed new ways of looking at the reimbursement landscape when bringing a therapy to market (read Mark’s recap here).

Richard Grant, Global Vice President of Cell Therapy at Invetech, focused on the importance of manufacturability, as well as ways to minimize cost of goods while still maintaining product quality. Below is a brief recap of the key points from Richard’s presentation. You can also watch the webinar recording in its entirety here.

Cell therapies show incredible promise for treating some of today’s most debilitating diseases. As a new therapy emerges, cell therapy companies must focus on efficacy—making sure the treatment is safe and effective for patients. But as they progress through clinical trials and move closer to commercial-scale production, the focus must shift to scalability, reproducibility and integrity of the product throughout the supply chain.

Without a doubt efficacy is crucial to the viability of a new cell therapy, but what happens next? As you gain confidence in your treatment and start thinking about scaling production, you’ll observe a dramatic change in manufacturing requirements and the rising importance of several key factors in the commercial production process.

The five areas that rise in importance are:

• Cost of goods
• Scalability
• Product quality
• Process integrity
• Regulatory requirements

Large-scale manufacturing requires solid quality control measures and repeatable processes. To achieve commercial-scale success and ensure a clearer path to FDA-approval, cell therapy companies need to error-proof the product manufacturing process as much as possible in order to reduce variability and ensure consistency, reproducibility and reliability throughout the process.

Human error or variability is a primary cause of inconsistency, disruption and loss in a manufacturing process. Rigorous QA processes can help reduce the risk of quality-related loss and exposure to criticism or restrictions in the industry, while automation can eliminate human error and variability within the process. Employing tactics like automated sequencing, error-proofing consumable loading, and controlled QC collection also help to keep quality levels high.

Costs decrease when operations are optimized, easily repeatable and efficient. Aside from automating processing, you can create repeatable steps and verify each one before and during the process. This is especially important to cell therapies as small changes in process can have unexpected effects on the integrity of the treatment.

In the healthcare industry, patients and practitioners must have complete confidence that the treatment they’re administrating is safe and not contaminated. There are several keys to ensure this as you scale manufacturing:

• Use of single-use disposables to prevent unwanted contamination while allowing the processing of multiple patient batches in common low grade clean space
• In-process QC testing for quality and repeatability

Most commonly, cell-based therapies are either allogeneic or autologous. In the former, where cells originating from a single donor provide treatments to large numbers of patients, increasing batch size or a single production facility’s capacity is “scaling up.” In the latter, each patient’s cells constitute a batch and will require more facilities and equipment to scale processing—this is “scaling out.” Each type requires careful attention to different sets of variables to maintain a stable and reliable manufacturing process.

New manufacturing processes can expose the treatment to new variables, and a strict process to define and maintain the product’s critical quality attributes (CQAs) can minimize any threats to efficacy. A great example of this is scaling up steps from clinical trial volume production to commercial scale, Steps such as expansion and harvest of an allogeneic therapy may need to be performed on pieces of equipment in an industrial scale manufacturing environment. How can you ensure the product’s quality throughout the journey? By carefully characterizing the product and its CQAs and monitoring the process to ensure that the cell journey through manufacturing is the same at both scales.

To have a reliable manufacturing process—and be approved by regulatory organizations—you must have evidence that it can consistently produce a quality product. You can test both the equipment producing your therapy through IQ, OQ and PQ of your manufacturing line and process and whether product quality is consistent from batch to batch and patient to patient (for autologous therapies) by analyzing data gathered during process development and comparing it with data gathered while manufacturing the product. Our comprehensive white paper on achieving commercial-scale success further dives into process validation.

Costs along the supply chain can hurt your profit margin and hinder scale. There are several ways to optimize costs without putting the integrity of your product at risk:

• Lower COGS by optimizing processes through use of single-use disposables, minimizing skilled labor through automation, and reagent and quality testing optimization.
• Optimizing use of equipment and facilities by minimizing high grade clean space and capital (facility and equipment) required and maximizing process throughput on the high-cost equipment.
• Using the most efficient logistics and administration tools to streamline operations and minimize waste.

Cell therapies are especially exposed to supply chain issues. Many variables can put the quality of the product at risk, with a fresh product both time and temperature of shipment are crucial for incoming patient samples and outgoing product, exceeding the specified ranges results in the degradation or loss of that shipment. Even with frozen product, while time is less critical, shipping within the specified temperature again is critical. Tightly controlling the process of administration to the patient at the clinic is also an important consideration, staff at each clinic must be trained and the site validated for high quality consistent delivery of the therapy to the patient.

When addressing logistics, aim for visibility into each stage of the supply chain, understand the best strategy for your treatment, and be prepared with solutions to common problems.

• Incoming logistics – Collection, shipping time and conditions
• In-process – Scheduling, Traceability, Fresh vs. Frozen
• Outbound – Fresh vs. Frozen, Centralized vs. Distributed
• Administration at clinical site – Training, Process Control

Successful commercialization of a cell therapy requires more than just proving safety and efficacy to the regulators. Although efficacy is important—without it, there is no therapy—it is critical for cell therapy companies to think beyond efficacy and have a plan in place for how they will successfully move from the clinic to commercial-scale production. To enable a successful progression to commercialization, each of the five essential elements—manufacturability, cost of goods, reimbursement, needle-to-needle logistics and efficacy—must be considered in order to build a solid foundation for a game-changing therapy.