Newsletter April 2025

In recent years, the therapeutic potential and application spectrum of nucleic acids have expanded significantly. These advances are accompanied by distinct scientific and regulatory challenges, reflected in an increasingly diverse landscape of approval pathways. For companies in the pharmaceutical and biotechnology industries, early strategic planning and collaboration with experienced partners offers the opportunity to streamline development processes, minimize regulatory hurdles, and keep costs and timelines under control. This is where BioSpring comes in—as a CDMO partner with deep expertise in regulatory requirements, supported by 28 years of experience in oligonucleotide manufacturing.

The transition to the late development phase—including Phase III, Process Performance Qualification (PPQ), and commercialization—marks a critical milestone, accompanied by a significant increase in both complexity and regulatory expectations. BioSpring supports its clients in navigating potential regulatory challenges by identifying product-specific classifications and regulatory implications early on. This differentiation is essential for defining an effective and compliant validation strategy. Defining key parameters early helps prevent costly and time-consuming changes in later stages of development. BioSpring, as an established global market leader for nucleic acid manufacturing and analytics, is well-equipped to handle biological variability and complex quantification. This translates into shorter development timelines and more regulatory clarity for clients.

Every successful validation program relies on a solid analytical strategy — that's why BioSpring applies a fit-for-purpose approach tailored to each project’s specific needs. In late-stage development, a robust analytical validation framework requires not only technical expertise but also close and effective collaboration between all involved functions. BioSpring emphasizes cross-functional cooperation between regulatory affairs, quality assurance, validation, QC, and production teams—ensuring seamless integration of analytical strategies into the broader development and manufacturing processes.

International guidelines, such as ICH Q2(R2) and the USP, are systematically integrated into the development process and aligned with the specific requirements of our clients. BioSpring’s broad regulatory experience spans numerous international markets, having successfully supported commercial programs approved in the U.S., EU, U.K., Japan, Brazil, Saudi Arabia, China, and many others. This global perspective allows us to confidently guide our clients through complex regulatory requirements and deliver high-quality solutions that meet regional standards across the world. The key value added for clients is reliable, data-driven and collaborative project execution. With early regulatory guidance, well-founded specifications, a robust impurity control strategy, and platform technologies, BioSpring can help therapeutic nucleic acid programs move faster, mitigate risks, and reduce costs.

This Month's service in focus

Regulatory & CMC Support

Regulatory compliance is a critical factor in the successful development and commercialization of nucleic acid therapeutics. Navigating the complex landscape of global regulations requires expertise, precision, and a proactive approach. At BioSpring, we offer comprehensive Regulatory Support Services designed to streamline your approval process, minimize risks, and accelerate your path to market.

With decades of experience in GMP manufacturing, analytical services, and regulatory compliance, we understand the challenges biotech and pharma companies face. Our dedicated team of experts provides tailored solutions to ensure your regulatory filings are complete, accurate, and aligned with industry standards - helping you avoid costly delays and regulatory hurdles.

At BioSpring, we are more than just a service provider - we are your strategic regulatory partner. By leveraging our expertise, you can focus on innovation while we ensure your regulatory pathway is clear, efficient, and risk-free.

To learn more, visit our regulatory support page or contact us directly.

Regulatory Support For Filing:

Support in preparation of Scientific Advice Meeting
Writing of quality-related dossier sections (e.g., Module 3)
Review of regulatory submissions (IND, IMPD, NDA, MAA, J-NDA, BLA...)
Timely preparation of responses to regulatory questions from authorities
Assistance for post-approval life-cycle management

Additional Support:

Strategies for implementation of ICH M7 requirements & preparation of statements
- Implementation & development of purge factor approach (Purge & Fate Assessment)
- Support adapted to early- and late-development needs
Nitrosamine risk assessments
E&L Risk Assessments
Assistance with future platform knowledge submission

At this year’s CRISPR MEDiCiNE conference, Dr. Philipp Kamm, Project Lead for mRNA Manufacturing, presented BioSpring’s latest advancements in the production of long RNA molecules – such as pegRNAs and epegRNAs – highlighting our innovative approach to overcoming the challenges of traditional linear synthesis.

As the demand for increasingly complex and highly-pure nucleic acids continues to grow, so does the need for more efficient and scalable production technologies. While solid-phase synthesis remains a widely used method, it can face limitations as sequence length increases, with especially with maintaining overall yield and purity across extended synthesis cycles.

To tackle this, BioSpring has implemented a hybrid strategy that combines the precision of chemical synthesis with the flexibility of enzymatic ligation. Short RNA fragments are first synthesized chemically and then ligated enzymatically – either with or without a DNA template—to assemble the full-length product.

This integrated strategy offers new advantages, particularly when it comes to very long or structurally demanding sequences. By reducing the number of chemical steps required per strand, cumulative yield losses can be mitigated, leading to improved overall yields while maintaining the high product quality and integrity that BioSpring is known for.

With our continued investment in innovation and technology, we aim to set new standards in long nucleic acid production – empowering our clients to develop more effective therapies and have increased confidence in their success, providing our clients a strategic edge in the fast-moving world of synthetic biology and gene editing.

To learn more, don't hesitate to contact us.

In case you missed it: In our latest application note in collaboration with Waters, we investigated the possibility of confirming siRNA sequences using a denaturing and non-denaturing LC-MS method combined with the latest bioinformatics tools. To this end, we conducted a comparative analysis of the BioAccord and Vion IMS QTof systems to highlight the advantages of both platforms. Our results show that sequence confirmation can be achieved on both systems using different methods, while yielding comparable results.

siRNA play a pivotal role in the therapeutic treatment of genetic diseases, including hemophilia. They inhibit the translation of pathogenic proteins and are small double-stranded RNA molecules with a length of 20 to 25 bases. To ensure therapeutic efficacy, it is essential to confirm the sequences of the sense and antisense strands of the active duplex molecule.

For more information, please refer to the full application note available here.

Jérôme studied Biology and Physiology in France before earning his PhD Jérôme Mordel at the University of Strasbourg in cooperation with the Max Planck Institute in Frankfurt. After completing an advanced training seminar in life science management, he worked in the regulatory affairs department, covering both drug substance and drug product manufacturing. He joined BioSpring in January 2022 as a Regulatory Affairs Manager and now supports clients with phase-appropriate regulatory submissions including IND, IMPD, NDA, MAA, J-NDA, and BLA.

What do you like about your work?

"The variety of tasks in my job requires interaction with many different departments at BioSpring. Since we are involved in change management across various projects, we stay well-informed about what is happening throughout the company. I find it rewarding to see the continuous improvements that different teams develop and implement which aid our clients in accelerating their therapies to market and beyond. I also appreciate our close communication with clients—understanding their perspective and contributing to their regulatory submissions is very fulfilling."

How have your studies prepared you for working at BioSpring?

"Working on a PhD is a challenge—you need to stay organized and be able to precisely document your work based on existing data. That is similar to preparing regulatory documents for our customers. During my studies, I also had to respond to reviewers’ feedback, which is a comparable process. The main difference is the teamwork: here, colleagues contribute significantly and complete much of the preparatory work in advance."

What are your daily challenges as a Regulatory Affairs Manager?

"No two days are the same in regulatory affairs. Besides juggling different projects and keeping our customers informed about relevant updates to their products, we also help prepare the quality-related parts of regulatory submissions. The key is to provide just the right amount of information, depending on the project's development stage. Sometimes, customers forward questions from authorities at very short notice—and responding in time can be challenging."

Can you share a memorable project or accomplishment during your time here?

"One of our clients recently received marketing authorization for their product—a great achievement that reflects collaborative work across all departments at BioSpring. Even in the final steps of the process, BioSpring supported the customer by performing studies, providing critical data, informing them about changes, reviewing submission documents, and responding to regulatory questions. When a customer succeeds in bringing a treatment to patients, it is a success for BioSpring, too."

What makes your work unique?

"The regulatory landscape governing the manufacture of oligonucleotide-based products supported by BioSpring is evolving rapidly, driven by the growing number of approved RNA-based therapies. BioSpring not only implements current regulations with great proficiency but also plays an active role in shaping the regulatory frameworks of the future. It is inspiring to be part of a company that is both attuned to today’s requirements and engaged in shaping the standards of tomorrow."

What do you like to do in your free time?

"Since the birth of my son last year, I try to spend as much free time as possible with my family. That said, I still make room for some of my favorite hobbies—reading, cooking, and gardening—which I hope to share with my son as he grows up."

More Information, Easier Navigation - Our Website Update

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Whether you're looking for details on manufacturing, analytics, or our integrated services, our updated site helps you get the right information—quickly and effortlessly.