Analytical Platforms: The Foundation Of The Next Generation Of RNA Therapeutics

By Andreas N. Kuhn, Ph.D., Senior Vice President RNA Biochemistry & CMC Development, BioNTech SE, and Jan Falcke, Senior Director AS&T Projects & Strategy, BioNTech SE

The first generation of RNA therapeutics proved that messenger RNA could become a viable pharmaceutical modality. The next generation will be defined by something different: our ability to characterize, understand, and control increasingly complex RNA products throughout their entire lifecycle.

During the past decade, remarkable advances in RNA sequence engineering, delivery systems, manufacturing technologies, and clinical development have transformed RNA from an experimental concept into one of the pharmaceutical industry's most dynamic therapeutic platforms. Yet as the field matures, the challenges confronting developers are evolving. Scientific innovation continues to accelerate, but the ability to consistently translate that innovation into scalable, manufacturable, and globally accessible medicines increasingly depends on analytical science.

For many organizations, analytical development has traditionally been viewed as a supporting function — a collection of release assays, validation activities, and quality control tests necessary to satisfy regulatory expectations. That perspective is becoming outdated.

Analytical science is emerging as one of the primary strategic drivers of technology platform development. It influences manufacturing flexibility, technology transfer, lifecycle management, regulatory confidence, and ultimately the speed with which new RNA medicines reach patients.

As mRNA therapeutics become more sophisticated, analytical platforms are no longer simply measuring product quality. They are becoming foundational infrastructure that enables innovation itself.

RNA Innovation Is Creating New Analytical Challenges

The RNA landscape is expanding well beyond first-generation mRNA vaccines. Developers are pursuing self-amplifying RNA, circular RNA, trans-amplifying systems, personalized cancer vaccines, RNA editing, gene-editing payloads, and increasingly complex combinations of RNA modalities with advanced delivery technologies.

Each innovation expands therapeutic opportunity, but each also introduces additional molecular complexity. Products differ in sequence architecture, nucleotide chemistry, untranslated regions, cap structures, poly(A) tail design, formulations, and manufacturing processes. Traditional development models, in which every new product receives an entirely independent analytical package, become increasingly difficult to sustain as portfolios expand.

The challenge facing the industry is therefore not simply how to develop better RNA molecules. It is how to build analytical systems capable of supporting entire classes of RNA products without rebuilding development infrastructure for every individual program. That shift represents one of the most significant transitions currently underway in pharmaceutical development.

From Product Thinking To Platform Thinking

Historically, analytical development has centered on individual products. Each candidate required its own analytical procedures, validation studies, characterization strategy, and control framework. While scientifically rigorous, this approach often treats every new molecule as though development begins from zero.

Applying platform concepts approaches the problem differently. Rather than asking how to characterize a single product, development of an analytical platform technology asks what knowledge can be leveraged across many related products. Shared manufacturing principles, recurring critical quality attributes, common analytical methodologies, and accumulated process understanding become reusable scientific assets rather than isolated project experience.

Recent regulatory guidance reflects this evolution. The updated ICH Q2(R2) guideline, together with ICH Q14 and emerging USP <1220> concepts, emphasize lifecycle-based analytical development built upon scientific understanding, the incorporation of knowledge gained from QC routine testing, and risk-based decision making rather than validation as a single static event.

Knowledge generated during development of one product becomes the foundation for future products. Routine manufacturing continues to expand that knowledge base. Every commercial campaign strengthens confidence in the analytical platform itself. In this framework, platform analytical procedures become dynamic systems that improve over time rather than fixed procedures established once and rarely revisited thereby enhancing method robustness and reliability.

Building Regulatory Confidence Through Knowledge

Regulators ultimately seek confidence that products are consistently manufactured, appropriately controlled, and scientifically understood. Analytical understanding has therefore become one of the strongest enablers of regulatory acceleration. Rather than relying exclusively on repeated validation exercises, regulators increasingly encourage developers to demonstrate comprehensive understanding of analytical performance throughout the product lifecycle. This evolution changes the purpose of analytical development.

Instead of simply generating sufficient data for regulatory submissions, analytical organizations are building knowledge that supports manufacturing changes, technology transfer, comparability exercises, lifecycle improvements, and future product variants. Scientific understanding becomes a reusable regulatory asset.

For platform technologies such as RNA therapeutics, where successive products often share manufacturing processes, formulation strategies, and analytical methodologies, this accumulated knowledge has extraordinary value.

RNA Integrity: A Practical Example Of Platform Analytics

One example illustrates how platform thinking is already transforming RNA development.

RNA integrity, generally defined as the percentage of intact, full-length mRNA, represents one of the most important critical quality attributes for in vitro transcribed RNA. Degradation, leading to lower integrity, directly influences product stability, efficacy and manufacturing consistency.

Capillary gel electrophoresis (CGE) has become a widely used analytical technique for evaluating RNA integrity by separating intact RNA from fragmented species and quantifying degradation profiles. While this method initially served individual development programs, platform-based analytical development demonstrates how the same analytical procedure can be successfully applied across diverse RNA products sharing common molecular characteristics.

Rather than developing entirely new RNA integrity assays for every candidate, developers can build on establish validated analytical procedures across different products and ultimately generate a substantial body of data and knowledge cover a broad sequence space, including modified and unmodified mRNA, multiple cap structures, diverse untranslated regions, varying poly(A) tail designs, and a wide range of transcript lengths. This might be particularly relevant for individualized approaches, for which mRNA is especially well suited. In such settings, patient-specific sequences are designed and manufactured, requiring analytical methods that are applicable across the whole product-space.

As knowledge accumulates across successive programs, analytical data grows. Instead of repeatedly asking whether an assay works for a new molecule, developers increasingly ask whether existing scientific knowledge (=data) already supports its application. That distinction fundamentally changes development strategy.

Risk Assessment Replaces Reinvention

Platform analytical procedures do not eliminate scientific rigor; they redirect it. When a new mRNA product enters development, the central question is no longer whether every analytical method requires redevelopment. Instead, developers perform structured risk assessments evaluating differences in manufacturing processes, molecular characteristics, formulation, analytical performance, and intended use.

Existing knowledge is reviewed; historical performance is examined; and trending data from routine manufacturing provides additional confidence. Only where data and scientific knowledge are missing supplemental validation studies are required. This approach preserves analytical rigor while avoiding unnecessary duplication of work.

For rapidly evolving RNA platforms, particularly those supporting variant-adapted vaccines or successive therapeutic generations, such flexibility has the potential to dramatically shorten development timelines without compromising quality.

Comparability Is Becoming A Competitive Advantage

One of the defining characteristics of RNA therapeutics is continuous innovation. Manufacturing processes improve; analytical technologies evolve; and facilities expand. Raw materials change; delivery systems mature; and development does not stop once clinical trials begin.  To preserve platform applicability, however, changes should be introduced in a controlled manner and thoroughly evaluated. Accordingly, predefined core elements of the manufacturing process and analytical methods should remain consistent. Organizations must therefore continually demonstrate that products manufactured today remain comparable to those evaluated during earlier development stages.

Strong analytical platforms make this possible. Rather than viewing comparability as an isolated “checking the box” exercise, developers can tap into deep product understanding from the earliest stages of development, allowing future process changes to be evaluated within an established scientific and risk-based framework. In this way, accumulated knowledge can support more efficient and targeted comparability assessments, while still ensuring that appropriate evidence is generated to demonstrate continued product quality.

This capability is often characteristic of more mature development organizations, which can leverage platform knowledge and lifecycle data rather than relying exclusively on product-specific approaches.

Analytical Science Is Becoming A Business Strategy

For years, organizations competed on discovery. Today, they increasingly compete on development efficiency. The ability to move a platform technology from discovery into manufacturing without repeatedly rebuilding analytical infrastructure can affect timelines, regulatory interactions, technology transfer, lifecycle costs, and ultimately return on investment. Analytical capability is no longer simply a laboratory function. It has become a strategic business capability.

Commercial Manufacturing Rewards Applying Platform Concepts

The value of platform concepts extends beyond development. Commercial manufacturing continuously generates additional knowledge through in-process and routine testing, trending analyses, deviation investigations, and lifecycle management activities.

Every manufactured batch contributes data. Every analytical result strengthens process understanding. Over time, technology platforms become increasingly robust because they are informed by real-world manufacturing experience rather than development studies alone.

This creates an important feedback loop in which development generates knowledge, commercial manufacturing expands that knowledge, and lifecycle management continuously refines analytical understanding.

Future products benefit from the accumulated experience of previous ones. In many respects, knowledge itself becomes one of the most valuable products organizations create.

The Future Will Be Data-Driven

As analytical technologies continue to advance, organizations are generating unprecedented volumes of information.

Examples include the following:

• High-resolution sequencing
• Advanced structural characterization
• Mass spectrometry
• Biophysical analysis
• Digital manufacturing systems, and
• In-Process analytical technologies.

The challenge is no longer obtaining data. It is curating the data and determining which data truly matters.

Artificial intelligence and machine learning will increasingly assist researchers in extracting meaningful insights from these multidimensional datasets, identifying relationships that may remain hidden through conventional analysis.

Importantly, computational tools will not replace scientific judgment. Instead, they will enhance our ability to understand how molecular structure, manufacturing processes, analytical measurements, and biological performance interact across increasingly complex RNA platforms.

The convergence of analytical science, computational biology, and manufacturing data promises to accelerate both product development and regulatory decision-making.

Looking Ahead

The first decade of RNA therapeutics demonstrated that messenger RNA could become medicine. The next decade will determine whether RNA becomes a truly industrialized pharmaceutical platform.

Achieving that vision will require more than innovative biology. It will require analytical systems capable of supporting successive generations of products, facilitating technology transfer,  and continuously expanding scientific understanding throughout the product lifecycle.

Analytical platforms represent far more than operational efficiencies. They enable organizations to leverage accumulated knowledge across diverse development programs, accelerate new product introductions, increase robustness, and support commercial scalability without sacrificing scientific rigor thereby  enhancing product quality.

The future of RNA therapeutics will not be determined solely by the molecules we design. It will be determined by how effectively we implement them into the integrated manufacturing and analytical ecosystems that transform scientific knowledge into reproducible manufacturing, regulatory confidence, and ultimately patient access.

As RNA medicines continue expanding into increasingly complex therapeutic applications, analytical science is evolving from a supporting discipline into a strategic capability. The organizations that succeed will not simply generate better data. They will generate better understanding.

And in the next chapter of RNA therapeutics, understanding may become the industry's most valuable platform of all.

About The Authors

Jan M. Falcke, Ph.D., is Senior Director, Global Analytical Science and Technology at BioNTech SE, where he leads the Projects & Strategy team. In this role, he is responsible for shaping and advancing analytical control strategies for late-stage and commercial products, including mRNA-based products. With 10 years of experience across QC and CMC, Dr. Falcke has contributed to the development and commercialization of several mRNA products, with deep expertise in late-stage analytical development, analytical control strategy, and analytical lifecycle management. He brings strategic leadership across the full analytical product lifecycle, from late-stage development and launch readiness to commercial lifecycle support. Dr. Falcke holds a B.S. in Biology and an M.S. in Biochemistry and Molecular Biology from the University of Bremen. He earned his Ph.D. in Biology through the Max Planck Institute for Biology at the University of Tübingen.

Andreas Kuhn, Ph.D., has worked with RNA for almost thirty years. This started with his diploma and PhD theses on the structure and function of small non-coding RNAs using biochemical and molecular biology methods. In his post-doctoral work, Andreas studied RNA-protein interactions in the spliceosome in yeast and later worked on small molecules to affect pre-mRNA splicing. His work on mRNA-based immunotherapies began in 2007 in the academic group of Ugur Sahin at the University Clinic Mainz, and Andreas joined BioNTech SE shortly after its founding in 2008. In his current role as Senior Vice President RNA Biochemistry & CMC Development the main focus is expanding proprietary technologies to increase the efficacy of mRNA-based therapies and to develop and optimize GMP-compatible manufacturing processes and analytical methods for RNA. He has co-authored numerous publications and patents ranging from basic research on RNA to its application as a therapeutic agent and vaccine.