Q&A: Robust supply chains and global networks are among key considerations when choosing an mRNA CDMOQ&A: Robust supply chains and global networks are among key considerations when choosing an mRNA CDMO

In November, contract development and manufacturing organization (CDMO) Lonza announced the expansion of its bioconjugation facilities in Visp, Switzerland, wherein the firm pledged to add 200 jobs to two multipurpose suites by 2028.

In light of that announcement, BioProcess Insider sought insight from Torsten Schmidt, mRNA business unit head at Lonza to learn more about the challenges and innovations that are important to contract development and manufacturing organizations (CDMOs) and the biopharmaceutical partners that they work with. In this Q&A, Schmidt shares several insights relevant to the industry.

The conversation has been lightly edited for brevity and clarity.

BioProcess Insider (BPI): Going back a few years, what manufacturing challenges were revealed during the COVID-19 pandemic, and how have drug companies responded to them?

Torsten Schmidt (TS): The COVID-19 pandemic exposed several critical manufacturing challenges that required fast and strategic decision making to overcome.

The biggest challenge was the unprecedented immediate demand for COVID-19 vaccines, which necessitated a rapid scale-up of manufacturing processes and a high-speed ramp-up of manufacturing capacity. This presented significant technical and logistical hurdles. To address this, drug companies expanded their own facilities, adopted innovative technologies, and formed strategic partnerships with CDMOs to access specialized expertise, manufacturing capacity, and global infrastructure. This meant that we needed to expand our workforce globally at three sites to meet the growing demand for our mRNA services.

Another major challenge was the disruption of global supply chains for raw materials and critical components, leading to shortages and delays. To mitigate this risk, drug companies began diversifying their supply chains to reduce reliance on single-source suppliers.

With mRNA as an emerging modality, we also had to ensure that this new modality could be manufactured under the same robust quality-management systems as more established modalities. We did this by encouraging the transfer of talent, best practices, and knowledge from other modalities. It was amazing to witness the energy of the teams and their “can do” attitudes.

BPI: Can you discuss some of the manufacturing innovations that have recently helped improve drug design and processes?

TS: In recent years, there has been great progress in advanced analytical techniques such as mass spectrometry and chromatography, which enable precise characterization of drug substances and products. Most mRNA substances are encapsulated in lipid nanoparticles (LNP) to protect them from degradation and deliver them effectively to target cells. We are working with small biotech companies to explore several process development and manufacturing innovations, including LNP encapsulation. There are interesting applications that promise to meet stringent critical quality attributes while enabling high throughput cGMP manufacturing.

In addition, improvements in the mRNA encapsulation processes have also been contributing to advancing scalability and ensuring consistency of manufacturing processes. FDX Fluid Dynamix, Fraunhofer IPK, and Lonza developed a unique mixing device for producing nanoparticles and nanoparticle emulsions, precipitation processes, and many other mixing processes, leading to high yields with higher product quality through consistent nanoparticle size, morphology, and fewer filtration losses.

Looking ahead, the field continues to evolve, and the clinical potential of mRNA extends far beyond vaccines for infectious diseases. Expanding mRNA treatments to new therapeutic areas can be a game-changer. These innovations have led to improved drug stability, simplified supply chains, reduced costs, and increased accessibility to treatments.

BPI: What are some common misconceptions about drug manufacturing that companies should seek to avoid?

TS: A common misconception of CDMOs is that they operate in isolation, with limited collaboration between divisions. However, we at Lonza – as with some other CDMOs – take a fully-integrated approach. We foster collaboration across all our divisions through shared learnings and best practices to help provide a comprehensive, end-to-end offering for drug developers.

BPI: Similarly, what pitfalls can lead to companies failing when they try to enter the manufacturing space?

TS: The largest pitfall is the belief that the capabilities gathered during the manufacturing of prophylactic mRNA vaccines are sufficient to drive the modality to success at a wider scale. We believe that more investment is needed to unlock the full potential of this modality – and we have invested considerably to meet the unique challenges associated with mRNA manufacturing. Our focus has included – but is not limited to – hiring external experts, promoting internal talent from other modalities such as bioconjugation and analytics, in-licensing of innovative technologies, forging collaborations in manufacturing and analytics, and external partnerships for the characterization of new formulations.

BPI: How should drug companies approach regulatory bodies, and how can CDMOs help foster a productive relationship here?

TS: Drug companies, regardless of size, should establish early and open communication with regulatory agencies to streamline the approval process. They should also adhere to regulatory standards and cGMP and provide comprehensive data packages, thoroughly documenting all aspects of drug development and manufacturing.

Drug companies are turning to well-established CDMOs for support, especially small and emerging biotechnology companies. For these companies, establishing strategic partnerships enables access to additional supportive resources and in-depth expertise from the earliest stages of formulation, process, and clinical development to commercialization. CDMOs can assist by:

● Providing regulatory expertise: Leveraging their knowledge of regulatory requirements to guide drug development and manufacturing.

● Facilitating regulatory interactions: Acting as a liaison between the client and regulatory agencies.

● Ensuring compliance: Implementing robust quality-management systems to meet regulatory standards.

BPI: What technologies have emerged in the last three years or so that have changed the game for manufacturing?

TS: I believe the true game changers in mRNA manufacturing are still under development, and we are excited to be at the forefront of manufacturing innovation for this emerging modality. For example, we have onboarded a mixing technology for LNP manufacturing which offers remarkable improvements in scalability, robustness, and speed to contribute to more efficient and cost-effective manufacturing processes.

We are also implementing an industry-leading, real-time GMP quality control (QC) method for mRNA identity, integrity, and additional parameters with a UK-based biotechnology company. This collaboration enables a plug-and-play QC-ready test for simplified and faster release. Direct mRNA sequencing allows for simplified workflows, ultimately accelerating mRNA analytics.

BPI: What are the most important considerations that go into choosing the right CDMO for a project?

TS: In terms of mRNA production in a cGMP environment, the process is complex and costly. While capital investments in equipment and facilities are lower compared to other modalities, the processes and workflows required for sustainable GMP manufacturing are considerable.

Partnering with a CDMO that has end-to-end mRNA manufacturing knowledge can add capacity and expertise to your projects and can deliver gram-scale GMP mRNA suitable for clinical and commercial programs.

So, when selecting a CDMO for an mRNA project, consider one that can leverage a global network and established supply chains to source materials from cGMP suppliers at competitive rates. At Lonza, we select equipment, production systems, and materials to optimize the manufacturing process for mRNA-based vaccines and therapeutics. Additionally, we provide guidance on technology selection to ensure products meet specific cost, efficacy, and safety standards.