Squalene is used in parenteral drug delivery in vaccine adjuvant systems. Adjuvants stimulate the body’s immune response to the active ingredient, making vaccines more effective. Up until now, the squalene used in pharmaceutical applications has been sourced from shark liver oil. But many shark species are endangered, and the loss of shark populations threatens marine biodiversity.
Evonik has developed PhytoSquene® - the first plant-derived squalene available in GMP (Good Manufacturing Practice) quality. PhytoSquene® is made from amaranth, which is a renewable feedstock, thereby eliminating the need for shark-derived squalene. Alongside ecological benefits it provides pharmaceutical companies with a secure supply of high and consistent quality squalene that is non-immunogenic and compliant with European Pharmacopoeia regulations (Ph. Eur. monograph 2805).
In this interview, Dr. Rima Jaber, Global Product Manager Lipids at Evonik Health Care, gives insights into the rationale for developing and manufacturing PhytoSquene®.
Q: Why did you decide to focus on squalene?
A: Evonik is committed to sustainability, and we recognize that there is a huge need to make pharmaceutical products more sustainable. One way we can do this is by offering plant-based excipients for drug delivery that are based on renewable feedstocks.
We chose to focus on squalene because pharmaceutical-grade squalene is currently sourced exclusively from sharks. It takes between 2,500 and 3,000 sharks to extract roughly a ton of product.1 By offering an alternative, we can reduce the need to hunt sharks for squalene and as a result help preserve shark populations. Many of these species, such as the spiny dogfish (Squalus acanthias) are endangered.
Another advantage of offering plant-based squalene is that we open options for patient groups that avoid animal derived products for ethical or cultural reasons.
Q: Why is squalene needed in adjuvant systems?
A: Vaccine adjuvants are important because they improve the immunogenicity of vaccines. This means that lower or less frequent doses of an active ingredient are needed. In an adjuvant system, squalene is blended into emulsions with surfactants and other lipids. Alongside functionality, squalene has a well-established safety profile and high tolerance, making it particularly suitable for adjuvant formulations.
Q: Apart from the ecological aspect, are there other disadvantages to animal-derived squalene?
A: Squalene derived from animal sources, particularly shark liver oil, is associated with several risks. These include batch-to-batch variations and inconsistent quality, which can complicate regulatory processes and create uncertainty for manufacturers.
Q: Tell me more about your raw material amaranth
A: We make PhytoSquene® from the herbaceous plant amaranth (Amaranthus caudatus). Amaranth can be grown in many regions of the world because it can be cultivated in temperate climates. The growing time for amaranth until harvest is around 90 days, which is faster than for some other plant sources that could be used to make squalene.
Q: How is PhytoSquene® manufactured?
Squalene is obtained from amaranth oil, which is extracted from the seeds of the amaranth plant. This oil undergoes several enrichment and purification steps to meet the specifications outlined in the Ph. Eur. Monograph 2805. The production process for PhytoSquene® meets GMP standards, ensuring the high-quality necessary for pharmaceutical applications.
Q: You already told us about sustainability benefits, but does PhytoSquene® offer advantages over animal-derived squalene?
A: Beyond its environmental benefits, PhytoSquene® has a number of advantages. Many sharks are contaminated with methylmercury, which can cause regulatory complications. Plant-derived squalene does not face this issue. There is also higher batch-to-batch consistency in plant-derived squalene in comparison to animal-derived squalene. This also helps simplify regulatory processes.
As amaranth can be grown in many regions of the world, it is easier to ensure a secure supply of PhytoSquene® than of shark-derived squalene, which depends on the number of sharks caught and is likely to become increasingly unreliable as shark populations further decline.
Q: Is there anything else you would like to add?
A: We see that there is a demand for a secure commercial supply of squalene for pharmaceutical applications. By offering a plant-based solution, we can help pharmaceutical companies reduce dependency on animal-derived products.
We look forward to working with pharmaceutical partners to bring patients safe and effective vaccines, while preserving biodiversity.
Want to learn more about PhytoSquene®? Visit Evonik’s website