Modular and tunable alternative surfactants for biopharmaceuticals provide insights into Surfactant's Structure-Function relationship.

Surface-induced aggregation of protein therapeutics is opposed by employing surfactants, which are ubiquitously used in drug product development, with polysorbates being the gold standard. Since poloxamer 188 is currently the only generally accepted polysorbate alternative, but cannot be ubiquitously applied, there is a strong need to develop surfactant alternatives for protein biologics that would complement and possibly overcome known drawbacks of existing surfactants. Yet, a severe lack of structure-function relationship knowledge complicates the development of new surfactants.

Not the Usual Suspects: Alternative Surfactants for Biopharmaceuticals.

Therapeutically relevant proteins naturally adsorb to interfaces, causing aggregation which in turn potentially leads to numerous adverse consequences such as loss of activity or unwanted immunogenic reactions. Surfactants are ubiquitously used in biotherapeutics drug development to oppose interfacial stress, yet, the choice of the surfactant is extremely limited: to date, only polysorbates (PS20/80) and poloxamer 188 are used in commercial products. However, both surfactant families suffer from severe degradation and impurities of the raw material, which frequently increases the risk of particle generation, chemical protein degradation, and potential adverse immune reactions.

An Intra-Company Analysis of Inherent Particles in Biologicals Shapes the Protein Particle Mitigation Strategy Across Development Stages.

To better understand protein aggregation and inherent particle formation in the biologics pipeline at Novartis, a cross-functional team collected and analyzed historical protein particle issues. Inherent particle occurrences from the past 10 years were systematically captured in a protein particle database. Where the root cause was identified, a number of product attributes (such as development stage, process step, or protein format) were trended.

Controlled release of therapeutic antibody formats.

The local administration of antibodies can represent in many cases a significant improvement for antibody-based therapies. The benefits of local delivery include high drug concentrations at the target site, the possibility of lower drug dosing and less systemic drug exposure. Currently, the most relevant delivery sites for therapeutic antibodies are the posterior segments of the eye, mucosal surfaces, the articular joints and the central nervous system (CNS).

Pharmacokinetics, biocompatibility and bioavailability of a controlled release monoclonal antibody formulation.

The sustained and localized delivery of monoclonal antibodies has become highly relevant, because of the increasing number of investigated local delivery applications in recent years. As the local delivery of antibodies is associated with high technological hurdles, very few successful approaches have been reported in the literature so far. Alginate-based delivery systems were previously described as promising sustained release formulations for monoclonal antibodies (mAbs).

Understanding the freezing of biopharmaceuticals: first-principle modeling of the process and evaluation of its effect on product quality.

Freezing and thawing are important process steps in the manufacture of numerous biopharmaceuticals. It is well established that these process steps can significantly influence product quality attributes (PQA). Herein, we describe a physico-mathematical model to predict product temperature profiles based on the freezing program as input parameter in a commercial freeze-thaw module.

The role of polysorbate 80 and HPβCD at the air-water interface of IgG solutions.

Purpose: To test the hypothesis of surface displacement as the underlying mechanism for IgG stabilization by polysorbates and HPβCD against surface-induced aggregation.

Methods: Adsorption/desorption-kinetics of IgG-polysorbate 80/-HPβCD were monitored. Maximum bubble pressure method was used for processes within seconds from surface formation.

Protein stabilization by cyclodextrins in the liquid and dried state.

Aggregation is arguably the biggest challenge for the development of stable formulations and robust manufacturing processes of therapeutic proteins. In search of novel excipients inhibiting protein aggregation, cyclodextrins and their derivatives have been under examination for use in parenteral protein products since more than 20 years and significant research work has been accomplished highlighting the great potential of cyclodextrins as stabilizers of therapeutic proteins. Oftentimes, the potential of cyclodextrins to inhibit protein aggregation has been attributed to their capability to incorporate hydrophobic residues on aggregation-prone proteins or on their partially unfolded intermediates into the hydrophobic cavity.

Inhibition of agitation-induced aggregation of an IgG-antibody by hydroxypropyl-beta-cyclodextrin.

In order to provide an alternative to nonionic surfactants as excipients for protein formulations, cyclodextrin-derivatives (CDs) were examined for their potential to inhibit agitation-induced aggregation of an IgG in aqueous solution. Loss of monomeric protein and protein aggregation were monitored throughout the agitation experiments by size exclusion chromatography. Hydroxypropyl-beta-cyclodextrin (HPbetaCD) completely suppressed IgG-aggregation at a remarkably low concentration (2.