Lyophilized formulations for biologic drug stability

Biologics are typically administered via injection and are thus best designed as liquid parenteral solutions. However, maintaining the stability of liquid biological products can be challenging. 

Many protein types, including monoclonal antibodies, multispecific antibodies, antibody fragments, fusion proteins, bioconjugates, and recombinant proteins, are unstable in solution at room temperature or in the refrigerator.

Lyophilization (freeze-drying) can help solve this problem by producing stable lyophilized cakes that can be reconstituted at the point of administration.

Using a frozen liquid format for therapeutic products may appear to be a viable option for accelerating development and lowering initial costs in early-stage initiatives. However, the complexities of creating a frozen liquid formulation are often underestimated.

The related issues can increase hazards, result in longer timescales, and require a more resource-intensive strategy than using a lyophilized format.

Short to long-term challenges include selecting inappropriate storage conditions, selecting robust freezing conditions, a lack of molecule or excipient stability in frozen solutions for certain formulations, and compromising the integrity of the container closure system at ultralow temperatures.

The need for very low temperatures raises substantial challenges throughout the supply chain, particularly in terms of the logistics and facilities required for inspection, storage, monitoring, and distribution.

In addition, frozen liquids are not the most practical or competitive format for scaling up biologics during commercialization. As a result, it may be necessary to move to a liquid or lyophilized product during late-phase development, which will add significant effort, expense, and time to the program.

Acknowledgments

This article has been produced using materials originally authored by:

  • Maria Fernanda Zuluaga: Principal Scientist, Formulation Development, Integrated Biologics, Lonza
  • Christos Theodorou: Senior Scientist, Drug Product Process Development, Integrated Biologics, Lonza
  • Fabio Montagner: Strategic Project Lead, Pharmaceutical Services, Integrated Biologics, Lonza
  • Pedro Marques: Senior Analytical CMC Expert, Integrated Biologics, Lonza

About Lonza

Lonza is one of the world’s largest contract development and manufacturing organizations (CDMOs) dedicated to serving the healthcare industry. Working across five continents, our global team of approximately 20,000 colleagues works alongside pharma and biotech companies to turn their breakthrough innovations into viable therapies. We support our customers in bringing life-saving and life-enhancing treatments to patients worldwide with a combination of cutting-edge science, smart technology, and lean manufacturing.

Our company generated sales of CHF 6.5 billion with a CORE EBITDA of CHF 2.1 billion in Full-Year 2025.

Find out more at www.lonza.com.


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Last updated: May 4, 2026 at 4:28 AM

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