A  critical objective of any drug development program is to create faster-to-clinic stable formulations. Maximizing the stability of a therapeutic protein, peptide or vaccine is not an easy task. The use of recombinant albumin has the potential to bring valuable yet initially unstable, hard-to-formulate drug candidates to market. By providing improved dose control through protection against non-specific surface adsorption and reduction of unwanted immunogenicity through inhibition of aggregation and prevention of oxidation, recombinant albumin offers drug developers new potential for creating faster-to-clinic biological drugs and vaccines. 

Drug Development Challenges
Modern pharmaceuticals are changing. The industry is moving towards more complex molecules, such as antibody drug conjugates, vaccines and cell-based therapies and this presents formulation challenges. Formulation of hard-to-stabilize biologics is not a simple task. Issues can include physical degradations—aggregation/fibrillation, adsorption/depletion, unfolding, solubility/precipitation—and chemical degradations—oxidation, deamidation, truncation/degradation, hydrolysis.

Manufacturers are confronted with countless challenges during the formulation of novel drug classes. For instance, formulating antibodies to very high concentrations escalates the probability of products undergoing stability issues. Modified peptides and proteins with altered sequences and/or additional non-natural amino acids can also present stability issues. Additionally, highly active potent drugs, such as growth factors and hormones, often require dosing at very low levels, making dose control critical and difficult to achieve.
Aggregation and depletion of proteins and peptides in drug formulations is a major source of dosage form and storage instability. The presence of aggregates and sub-visible particles also compromises the safety and efficacy of the drug formulations and may lead to a series of problems during manufacturing, handling and post administration. As such the minimization of protein aggregation and chemical degradation is part of a de-risking strategy key to ensuring a smoother “developability” of a biopharmaceutical.

Standard formulation technologies do not offer the required stabilization capabilities for today’s advanced, complex therapeutics. For instance, lipids present in vaccine and cell-based therapies can be broken-up by standard excipient approaches and using detergents are ineffective. Products that require high concentrations can be limited by viscosity issues and the incidence of multiple issues, such as aggregation and oxidation occurring simultaneously, is common. Excipients that can mitigate multiple issues would bring significant benefits, and this is where the use of albumin in formulation represents a welcome alternative to traditional strategies.

The Albumin Answer
Human albumin, the most abundant carrier protein in plasma, constitutes 60% of total plasma protein. In the human body, albumin is responsible for the maintenance of oncotic pressure, plasma pH and the distribution of a variety of endogenous and exogenous ligands. Seventeen disulphide bonds give the albumin molecule excellent stability and resilience to environmental stress. It also contains multiple ionic and hydrophobic binding sites, where chemicals bind and are consequently transported around the body. Albumin is widely used in the manufacture of drug, vaccine, and device products for a range of applications such as formulation, drug delivery, and medical device coating.

Albumin offers a relatively simple solution to traditional strategies that require multiple stabilizers, or new strategies that require considerable experimentation before the point of formulation can be reached. It readily adsorbs to both hydrophobic and hydrophilic surfaces preventing non-specific adsorption of biopharmaceuticals during manufacture, formulation and storage. By dispersing uniformly in a solution it affords an insulating quality that minimizes physical drug instability and protein-protein interactions. As it has several different binding pockets, albumin can also interact with a diverse range of products and thereby stabilize them. These multiple mechanisms mean that albumin can stabilize products in a variety of situations and stresses.

Recombinant Albumin In Use
Although serum derived (human or bovine) albumin has been widely recognized as an effective stabilizer for many years, it has suffered a decline in popularity due to regulatory preference (concerns over blood-borne contaminants) for animal origin-free options. Today, with the availability of recombinant albumin, this is no longer an issue.

High-quality, animal origin-free recombinant human albumin, approved for use in the manufacture of human therapeutics, acts as an effective versatile stabilizer with the ability to protect challenging drug, cell and vaccine products from aggregation, non-specific adsorption, and oxidation. It enables drug developers to readily formulate otherwise instable drug candidates and to simplify their formulation strategy. As a result, albumin-enabled technology offers a fast, established pathway to the clinic and ultimately to market.

In use, recombinant albumin protects interferons against oxidation and adsorption, while improving solubility and reducing the potential for aggregation. It contributes low immunogenicity, alleviates any co-aggregation due to increased purity and less contaminating high molecular weight material. Recombinant albumin offers easier handling and improved patient compliance by enabling reformulation from lyophilized to simple liquid formulations and contributes improved stability in both liquid and solid state for vaccine products, improving yields during the process of harvesting and processing viruses for vaccine preparation. It also provides batch-to-batch consistency.

Conclusion
Because of its capabilities, albumin-enabled technology can help provide otherwise impossible drug candidates with a fast and clear path to market, paving the way to better health. With wide-ranging applications in the areas of formulation, drug delivery and medical device coating, recombinant albumin has demonstrated proven advantages for challenging peptide and protein formulations, down-stream processing of viral vaccines, stem cell and immunotherapy culturing, sub-unit and viral-vector formulations, biocompatible surface-coating of medical devices, well as cell therapy preservation and formulation. 

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Phil Morton is the Chief Technology Officer heading up Albumedix technology group. He has more than 20 years’ experience in the biopharmaceutical industry within process and product development both in R&D and manufacturing environments. His experience ranges from developing and transferring purification processes, to formulation development and characterization of these processes and products. Phil holds a Ph.D. in Biochemical Engineering from Birmingham University and followed this with post-doctoral studies at Cambridge University.