Modernizing Your Way to Success in Cell and Gene Therapy Manufacturing

How times have changed since the first cell and gene therapy (CGT) product, Kymriah, was approved five years ago. Since then, what was once viewed by outsiders as a niche sector of biopharma has grown into the most rapidly expanding and investor-enticing product pipeline in the life sciences. There are now 1,300 companies actively involved in cell and gene therapy manufacturing¹ and 11 gene therapy medicinal products with valid marketing authorization.² With bluebird bio scoring the latest big win with an approval for its $3 million per-patient gene therapy Skysona, it’s clear that the CGT juggernaut is only gaining momentum.³

That’s not to imply that cell and gene therapy manufacturing is all about cashing in on a gold rush. Developers of these novel products are striving to create life-altering therapies that have the potential to expand beyond applications to ultra-rare diseases. But bringing innovative therapies to market requires CGT developers to possess three essential capabilities:

• Streamlined processes.
• Flexible systems.
• The scalability and manufacturing capacity needed to adequately support production, clinical trials, and approval processes.

The Critical Role of the Cell and Gene Therapy CMO

Companies unable to develop the necessary capabilities in house (i.e., almost everyone) are increasingly turning to contract manufacturing organizations (CMOs). Contract manufacturing is highly sought after throughout the cell and gene therapy space because - unlike the typical, mostly smallish biotechs that develop innovative CGT products - CMOs have the right mix of expertise and resources. As more gene therapy developers of all sizes are evaluating external manufacturing resources, adaptability and scalability are quickly becoming a cell and gene therapy CMO’s most appealing traits.

Why then, if agility and scalability are such valuable characteristics for a CMO to have, can’t more of them provide it (i.e., why is the current wait for cell and gene therapy CMO's manufacturing capacity 12-18 months?⁴). The short answer: demand. There’s been a dramatic rise in the need for more outsourced cell and gene therapy manufacturing. In fact, estimates show that 90% or more of cell and gene therapy manufacturing is now outsourced, compared with just 35% for traditional biologic therapies.⁵

The key to meeting the rising demand - in addition to increasing capacity - is streamlining the production and quality processes involved in cell and gene therapy manufacturing.

Raising the Bar for Cell and Gene Manufacturing and Quality Systems

Unlike most drug approvals that are more focused on the clinical side of development, product quality and manufacturing processes face more rigorous scrutiny in cell and gene therapy approvals. Reinforcing this point, Scott Gottlieb gave a now famous (in cell and gene therapy manufacturing circles, anyway) quote when he was commissioner of the U.S. Food and Drug Administration (FDA):

“In contrast to traditional drug review, where 80% of the review is focused on the clinical portion of that process, and maybe 20% is focused on the product issues, I’d say that this general principal is almost completely inverted when it comes to cell and gene therapy,” Gottlieb said. “The initial clinical efficacy is often established early, and sometimes in small series of patients. The more challenging questions relate to product manufacturing and quality.”⁶

Turning more attention to manufacturing and quality is a logical approach. But it isn’t as easy as flipping a switch. Optimizing cell and gene therapy manufacturing and quality processes requires the right set of tools.

New 80/20 Ratio, New Cell and Gene Therapy Software Solutions 

Even though CGT developers are working on the cutting edge of scientific development, the production processes in place in most cell and gene therapy manufacturing environments are still performed manually using paper. But as CGT evolves, it’s clear that the old way of doing things isn’t compatible with modern needs. According to biopharma manufacturing professionals surveyed by BioPlan Associates, the most needed improvement in cell and gene therapy manufacturing is better process control/automation.⁷

The survey report’s authors noted that the most critical area where automation is needed in cell and gene therapy manufacturing is the digitization of production records that are presently maintained manually on paper.⁸ Automation can also help cell and gene manufacturers make significant improvements in other key areas, such as:

• Increasing the speed of process development and commercial products manufacturing.
• Lowering overall manufacturing costs.
• Supporting more consistent and better standardization of bioprocessing.

Knowing that the biggest strides can be made by implementing electronic batch records (EBRs) opens the door to more areas where quantifiable efficiencies can be gained. EBRs and other digitized production records don’t just offer more visibility into manufacturing processes and information that would otherwise be trapped in paper documents; they allow companies to capture and act on insights that will truly optimize production and contribute to continuous improvement efforts. And since regulators are more frequently requesting that records be digitized, EBRs just make good business and compliance sense.

Preparing for Success With Cell and Gene Therapy Software 

A cell and gene therapy software solution that digitizes production records enables you to bridge the gap between manufacturing and quality. A proven, robust solution can empower you with:

• Improved right-first-time metrics and the ability to perform comparative analyses.
• An overall reduction in deviations and corrective actions/preventive actions (CAPAs).
• Accelerated product releases.

To find out how your organization can benefit from a purpose-built software solution that digitizes production records, integrates essential processes, and unifies cell and gene manufacturing and quality systems, visit MasterControl’s Manufacturing Execution Simplified page.

References:

1. "Regenerative Medicine: Disrupting the Status Quo," Alliance for Regenerative Medicine, 2021 annual report.
2. "Gene Therapy Medicinal Products,” Paul-Ehrich-Institut, Federal Institute for Vaccines and Biomedicines, accessed Sept. 6, 2022.
3. "A $3M gene therapy: Bluebird bio breaks its own pricing record with FDA approval of Skysona,” Fierce Pharma, Sept. 19, 2022.
4. "Obstacles Preventing GMP Cell Therapy from Becoming Mainstream,” ThermoGenesis blog, Sept. 15, 2021.
5. "Cellular and Gene Therapies Face a Manufacturing Capacity Crunch,” by Ronald A. Rader, BioPharm International, Sept. 1, 2020.
6. "Remarks to the Alliance for Regenerative Medicine’s Annual Board Meeting,” speech by Scott Gottlieb, M.D., May 21, 2018.
7. "Cell & Gene Therapy Bioprocessing: Demand For Better Process Control, Expertise & CMOs,” by Ronald A. Rader and Eric S. Langer, Cell & Gene, May 14, 2021.
8. Supra note 7.