First-in-human clinical trial of allogeneic, platelet-derived extracellular vesicles as a potential therapeutic for delayed wound healing.

The release of growth factors, cytokines and extracellular matrix modifiers by activated platelets is an important step in the process of healthy wound healing. Extracellular vesicles (EVs) released by activated platelets carry this bioactive cargo in an enriched form, and may therefore represent a potential therapeutic for the treatment of delayed wound healing, such as chronic wounds. While EVs show great promise in regenerative medicine, their production at clinical scale remains a critical challenge and their tolerability in humans is still to be fully established.

C1q aggregate binding for the determination of anti-complementary activity of immunoglobulin products.

Aggregates in human immunoglobulin (Ig) products can develop due to employed manufacturing, formulation and storage conditions and can cause adverse reactions in patients. The test for anti-complementary activity (ACA) recommended by the European Pharmacopoeia (EP) is insensitive, variable and time consuming. We have optimised a commercial assay for the detection and quantitation of C1q binding aggregates in intravenous and intramuscular IgG preparations.

Effect of lobe pumping on human albumin: development of a lobe pump simulator using smoothed particle hydrodynamics.

Using SPH (smoothed particle hydrodynamics), the motion of a lobe pump under load was simulated in order to predict the level of shear stress experienced by a protein solution. By varying the gap size between the lobes and pump housing, variations in pump efficiency and shear stress were determined. The simulations indicated that pump shear was dependent on gap size, with shear stress levels (0-40 Pa) correlating with those estimated in previous albumin-pumping studies.

Effect of lobe pumping on human albumin: investigating the underlying mechanisms of aggregate formation.

A common problem in the manufacture of liquid protein therapeutics is the tendency for aggregation and particle formation on extended storage. One aspect of processing that might contribute to particle formation is pumping. In the present study, we demonstrate that lobe pumps can promote aggregation in albumin preparations.

Analytical techniques for the evaluation of liquid protein therapeutics.

A common problem in the manufacture of liquid protein therapeutics is the tendency for aggregation and particle formation on extended storage. Analytical techniques are required to study the propensity of solutions to form aggregates and particles and to allow the investigation of the effect of conditions encountered during manufacture and storage. A key challenge is to utilize appropriate specific and sensitive techniques to allow the early detection of initial aggregation events, thereby avoiding the need to resort to extended stability trials.