Not all albumins are created equal

Recombumin® to overcome challenges and embrace opportunities in virus-based therapies

As cutting-edge drugs such as viral vectors, cancer vaccines and oncolytic virotherapies make their way through the development pipeline, medical science stands on the brink of an unseen revolution. However, the life-changing potential of such innovative, virus-based therapies is not without challenges.

Virus diversity, which is the underlying property exploited to provide targeted clinical benefits, also represents a significant hurdle by precluding the application of a platform approach for downstream processing and formulation. There is a need for solutions to effectively apply across the spectrum of virus diversity, supporting the increasing demand for higher volume manufacturing of viral vectors, for improved logistics of distribution and end-use compliance.

At Albumedix, we believe recombinant human albumins (rAlb), and in particular the Recombumin® product portfolio, can provide the answers to many of these challenges and will allow developers – and patients – to embrace the opportunities opened up by this next generation of advanced biopharmaceuticals.

Challenges in next generation advanced biopharmaceuticals

The COVID-19 pandemic has demonstrated, if more proof was needed, the devastating impact of viruses on human health. But these complex, highly efficient structures have also been used to provide solutions, in the shape of life-saving vaccinations.

The use of these versatile assemblies has, during the years, expanded from treatment of infectious diseases into areas such as gene editing and cancer prevention/cure.

Despite setbacks suffered in the early days, progress has been fast, knowledge has accumulated, and lessons have been learned generating new modalities with improved safety and efficacy, which has led to a sharp increase in the development of viral vectors-based therapies. With an increasing number now approaching the market, and many in early phases targeting more wide-spread diseases, developers are facing a new set of production, manufacturing and stability challenges.

To date, marketed gene therapy products have been developed for rare diseases and are administered locally. But the desire to target a wider range of conditions, and much larger patient groups, underpins the need for systemic administration, with all the associated technical challenges. Manufacturers need to produce large volumes of doses to meet patient demand. To allow for systemic delivery the final product needs to be formulated at higher concentrations and the drug product needs to have an increased stability, to ease the supply chain and improve end-user compliance. All this adds huge complexity to downstream processes and formulation.

A tale of two human albumins

For gene therapy drug products, as with any drug product, purity, stability and batch-to-batch consistency are paramount considerations for a very good reason – they impact performance, efficacy, and safety.

Albumin, a multi-functional excipient with validated stabilization properties, can be key in ensuring consistency, maintaining the stability and efficacy of the drug product so that patients receive optimal treatment with maximum effect.

Albumin is a proven effective and versatile stabilizer that can protect protein, peptide, vaccine and cell therapy products from aggregation, surface adsorption, oxidation, and precipitation. In Albumedix, over the last few years we have seen an escalation in the number of customer enquiries within the viral vector space, with many resulting in a successful use Recombumin® due to the benefits provided for the given challenges.

However, not all albumins are created equal.

Albumin quality is essential to ensure batch-to-batch consistency of the drug product, but also, and very importantly, albumin stabilization potential can be altered by post translational modifications and by the presence of impurities and/or aggregates.

Only a highly pure albumin, like Recombumin®, allows the full exploitation of albumin potential with consistent results. Unlike plasma derived human serum albumin (HSA) and other recombinant albumins, Recombumin® offers a reliable albumin source with excellent batch-to-batch consistency and security of supply. Our products have extremely low levels of post translational modifications (PTMs), unsurpassed cGMP quality meeting USP-NF standards and have been commercially validated in marketed and late-stage clinical drug and vaccine candidates.

Therefore, Recombumin® is a natural choice when safety, efficacy and reliability are important. 

The natural solution

Albumin’s natural stabilization properties enable the formulation of challenging drug, vaccine and cell therapies. Albumin is considered a multi-functional excipient because it can protect unstable biopharmaceuticals with its multitude of beneficial functions at various stages of the development process.

Albumin readily adsorbs to both hydrophobic and hydrophilic surfaces in a single monolayer, preventing non-specific adsorption during manufacture, formulation and storage. We have demonstrated that just 1-2 mg of Recombumin® is needed to coat 1 m2 of surface. This property has been used by developers to:

• Increase the overall production yield by reducing losses during downstream processing
• Provide a safer dose control in the formulated product by minimizing losses on the container surfaces
• Prevent surface-induced denaturation, thereby cutting the risks of reduced efficacy and increased immunogenicity

Albumin not only binds to a wide range of compounds, using both ionic and hydrophobic interactions, but it also disperses uniformly throughout a solution.

Therefore, by one or the other mechanism, Recombumin® can be used to prevent aggregation or changes in higher order structure during manufacturing, handling and final formulation by protecting fragile particles from shear and temperature stresses, contributing to maintain potency and efficacy.

Albumin has one natural free thiol group, cysteine 34 (C34), which has been evolutionarily optimized to react with aggressive oxidizing species. When in formulation, this enables albumin to protect biopharmaceuticals against oxidative modifications. Our Recombumin® has the highest levels of free C34, when compared with other albumins (serum derived or recombinant), ensuring a consistent anti-oxidative potential.

Towards the future of viral vectors

Working with viruses presents as many challenges as it does opportunities. Many developers are eager to produce larger volumes of doses at higher concentration without compromising on safety, efficacy, purity, stability and batch-to-batch consistency.

The natural characteristics of albumin take the industry some of the way to overcoming such obstacles. It is left to the advanced properties of Recombumin® to take us over the line, and unlock the life-saving potential of next generation virus-based drug treatments.

Written by - 

Eleonora Cerasoli, PhD

Science Manager, Albumedix