SFF
mRNA-based drugs offer enormous potential for treating a wide range of diseases, but their inherent instability creates significant development and manufacturing challenges. Ensuring these delicate molecules remain effective through storage and transport is critical—and that’s where lyophilisation (freeze-drying) comes into play.
The Stability challenge
mRNA molecules are fragile. Their physical instability such as loss of structure, aggregation, and precipitation, can compromise their translation once administered. Chemically, they’re vulnerable to degradation from hydrolysis and oxidation.
Without the right stabilisation strategy, these therapies can end up with a short shelf life or require frozen or ultra-frozen transport and storage. This makes distribution complex and can limit access in regions without robust cold-chain infrastructure.
The Role of lyophilisation
Lyophilisation is a well-established technique used to improve the stability of temperature-sensitive drugs. By removing water through a combination of freezing and vacuum drying, it helps protect the integrity of the active ingredient without exposing it to damaging heat.
Key benefits of lyophilisation include:
- Optimised products shelf life
- Improved product stability in dry powder form
- Water removal without thermal degradation
- Fast, simple reconstitution before administration
Addressing formulation challenges
For lyophilisation to be effective with mRNA drugs, several key factors must be addressed:
- Ensuring product stability:
The final freeze-dried product (or “cake”) must be easily and consistently reconstituted without losing quality. This is especially important for low-dose mRNA drugs, where the small volume can make it harder to achieve a stable, uniform formulation. Cryo-protectants and bulking agents must be carefully chosen for compatibility and stability. - Preserving Lipid nanoparticles (LNPs):
Many mRNA therapeutics rely on LNPs to deliver their payload. The lyophilisation process must be fine-tuned to protect these lipid structures, often through longer, more controlled drying cycles that reduce physical stress on the nanoparticles.
Optimising the process
Gentle freeze-drying:
A detailed understanding of each stage—freezing, primary drying, and secondary drying—is essential. Accelerated cycles might save time but can risk damaging sensitive mRNA components.
Formulation adjustments:
Modifying buffer composition or ionic strength can enhance the cake structure and support better reconstitution. Pre-lyophilisation mRNA concentration can also influence the drying process. For LNP-based products, the addition of the right surfactants can help manage aggregation.
Notably, altering the structure of the mRNA itself is not advisable, as it risks undermining the treatment’s intended function.
Embracing technological advances
New technologies are improving the lyophilisation process. Automation in loading and unloading freeze-dried products speeds up production and limits exposure to non-ideal temperatures, helping maintain stability and product quality.
Start early for better outcomes
Building lyophilisation into the early stages of formulation development makes it easier to establish a robust and scalable process. For mRNA developers, starting early also means fewer surprises later in the pipeline—particularly as the therapy approaches commercialisation.
Many companies are now turning to CDMOs for support. These partners offer valuable experience in lyophilisation feasibility studies and process optimisation, drawing on insights from the rapid evolution of mRNA technology.
How Recipharm can support your lyophilisation journey
Recipharm is a leading CDMO with extensive experience in sterile pharmaceutical lyophilisation. We offer:
- A centre of excellence for vial-based lyophilisation, equipped with state-of-the-art, highly automated systems
- Full-service capabilities, from R&D-scale lyo cycle development and optimisation to seamless scale-up for commercial production
- Single-use (disposable) manufacturing options and a wide range of vial sizes, including ISO standards
- High-speed filling lines, automatic loading/unloading, and laser optic-controlled transfer systems for maximum efficiency
- Technical trials, packaging material testing, and CIP/SIP-compliant systems
- Unique, automatic movable crimping stations that enhance operational flexibility
With over 30 years of experience in lyophilisation and aseptic filling, Recipharm’s global network of facilities—certified by major regulatory authorities including the FDA, EMEA and other global markets—ensures consistent delivery and the highest quality standards.
Whether you're a biotech start-up or an established pharmaceutical company, Recipharm can tailor its services to your unique needs—supporting you at every step from development to commercialisation.
Ready to accelerate your mRNA therapy development with expert lyophilisation support? Get in touch with us today.