The Hidden Bottleneck In Advanced Therapies Isn't Science… It's Translational Friction
By William Soliman, Ph.D., BCMAS, founder & CIO, White Manna Capital
In his latest “Soliman Says,” Will Soliman turns his attention to one of the most underappreciated challenges facing RNA therapeutics, gene therapies, cell therapies, and other advanced modalities: translational friction. As innovative therapies move from discovery into clinical development and commercial manufacturing, operational complexity, scalability limitations, technology transfer challenges, and manufacturing execution frequently become the true determinants of success or failure.
As Advanced Therapies Mature, Manufacturing Readiness Is Emerging As The True Competitive Advantage
To those outside of the life sciences industry, advanced therapies have never looked more promising and indeed they are. RNA therapeutics, gene therapies, cell therapies, and other next-generation modalities are producing clinical results that would have seemed impossible just a decade ago. Scientific innovation continues to accelerate, driven by breakthroughs in molecular biology, delivery technologies, and computational design. But despite unprecedented scientific progress, many advanced therapy programs still struggle to reach commercialization. The reason often has little to do with the underlying science.
Increasingly, the greatest threat to success is translational friction. This refers to the operational and manufacturing challenges that emerge as promising discoveries move from the laboratory into clinical development and commercial-scale production.
While there are several factors that influence commercial success, manufacturing challenges and scalability can create obstacles that must be addressed early on in the process.
The Reality Behind Advanced Therapy Development
The biotech industry often celebrates discovery milestones: novel targets identified, delivery systems optimized, and encouraging early clinical data. What receives less attention are the practical realities that determine whether a therapy can be consistently manufactured, transferred, scaled, and delivered to patients.
For advanced therapies, the path from proof-of-concept to commercial readiness is significantly more complex than for traditional small molecules. The challenge is not simply creating a therapeutic that works but creating a therapeutic that works repeatedly, at scale, under regulatory scrutiny, and across multiple manufacturing environments and this is where we see translational friction beginning to emerge.
Scale-Up Is Where Complexity Multiplies
Many advanced therapies perform exceptionally well during early-stage development. However, processes that function efficiently in a research setting often behave differently when scaled for clinical or commercial production. Small variations in raw materials, process parameters, equipment configurations, or environmental conditions can create significant impacts on product quality and consistency.
For RNA-based therapeutics, these challenges are particularly pronounced. Manufacturers must maintain tight control over critical quality attributes while managing increasingly sophisticated delivery systems and production workflows. As production volumes increase, maintaining reproducibility becomes more difficult.
What appears to be a robust process in a laboratory may reveal hidden vulnerabilities during scale-up. This results in delayed timelines, increased development costs, and unexpected manufacturing investigations.
Process Drift Creates Invisible Risk
One of the most overlooked threats in advanced therapy manufacturing is process drift. Unlike catastrophic failures, process drift occurs gradually and can impact the success of the overall results a pharma manufacturer is looking to achieve.
A manufacturing process may remain within specification while slowly moving away from its original validated state. Over time, subtle changes in operators, suppliers, equipment, or procedures can introduce variability that eventually impacts quality, yield, or reproducibility. By the time organizations recognize the problem, significant resources may already have been invested. For emerging biotechnology companies operating under tight funding constraints, these surprises can be especially costly.
The takeaway is that process robustness must be designed into development programs from the beginning rather than addressed as an afterthought.
The CDMO Relationship Is Becoming a Strategic Differentiator
As advanced therapies become more complex, contract development and manufacturing organizations (CDMOs) play an increasingly critical role. However, outsourcing alone does not eliminate manufacturing risk and in many cases, challenges arise because technology transfer is treated as a transactional event rather than a strategic partnership. Successful programs require close alignment between sponsors and manufacturing partners from the earliest stages of development. This includes shared visibility into process parameters, quality considerations, scalability requirements, and future commercialization objectives.
When communication gaps emerge between development teams and CDMOs, translational friction increases dramatically and knowledge transfer becomes fragmented. This can lead to a situation where timelines slip, investigations increase and manufacturing surprises become more likely. Organizations that integrate CDMO partners early often discover potential scalability challenges before they become costly obstacles.
Manufacturability Should Not Be a Late-Stage Discussion
Historically, many organizations focused first on demonstrating biological efficacy and addressed manufacturing considerations later in development but that approach is becoming increasingly risky. Today's advanced therapies require manufacturability to be considered from the outset. Questions such as process scalability, analytical characterization, supply chain resilience, technology transfer readiness, and commercial manufacturing feasibility should be incorporated into early development decisions.
The most successful organizations increasingly view development through both scientific and operational lenses simultaneously. Rather than asking, "Can we make this therapy work?" They ask, "Can we make this therapy work consistently, reliably, and at commercial scale?" That distinction often determines which programs ultimately succeed.
Building a Competitive Advantage
Scientific innovation will always remain essential to advanced therapy development. However, as the industry matures, competitive advantage is shifting. Organizations that master translational execution — process development, manufacturing scalability, technology transfer, quality systems, and operational integration will increasingly separate themselves from competitors. The future of advanced therapies will not be determined solely by better biology. It will be determined by which organizations can most effectively bridge the gap between discovery and delivery.
Because in today's advanced therapy landscape, the greatest bottleneck is rarely scientific innovation itself bur rather the friction that occurs when innovation attempts to become reality.
About The Author:
William Soliman, Ph.D., is the founder & CEO of the Accreditation Council for Medical Affairs (ACMA) and the founder & CEO of White Manna Capital Partners, a biotech/pharma focused hedge fund. The ACMA is the leading life sciences accreditation, certification, and training company in the world and established the first ever certification standards for prior authorization, reimbursement, pharma sales, medical science liaisons, and medical affairs professionals. Soliman is considered a pharmaceutical industry futurist. In March 2021, he testified before the United States Congress’ Energy and Commerce Health Subcommittee about the pharmaceutical industry and the importance of professional standards for those who directly engage healthcare providers, like sales representatives. Soliman is a former pharmaceutical executive who held leadership roles at several Big Pharma companies, including Merck, Johnson & Johnson, AbbVie, and Gilead. He is routinely featured on media outlets such as NewsNation, Fox News, ABC News, Forbes, Al Jazeera, Yahoo! Finance, Yahoo! Business TV, and more. Soliman received his Ph.D. from Columbia University and his bachelor’s degree from New York University.