D3.191 - Demonstrating the Stability of Allergoids, the Next Generation of Allergen Therapy

A robust stability package is essential to ensure patient safety by ensuring products remain effective and of the highest quality throughout their shelf-life (ICHQ1A(R2), 2003). A stability trial involves assessing key quality attributes throughout the product lifespan and scrutinising the results against predetermined specification limits. 

PQ Grass (27600 SU) is an allergoid product where 13 different grasses have been modified to attenuate their ability to elicit an IgE response. The aim of the modification process is to reduce total allergenicity (IgE reactivity) while maintaining the antigenicity (IgG epitope potency) of the grass allergens. This modification allows for an increasedquantity of allergen to be included in the product while maintaining safety. 

Forced degradation is a process that involves degradation of the product at conditions more severe than typical accelerated conditions. Forced degradation studies (FDS) were carried out to determine the stability indicating capability of analytical assays for PQ Grass.

Antigenicity profile of PQ Grass is measured by an IgG based ELISA platform, and MPL congeners are monitored via HPLC for the duration of the stability study. The residual total allergenicity of PQ Grass is monitored throughout the stability studies to assure the process of IgE attenuation is stable.

Control samples were kept at the recommended storage condition, while test samples were exposed to thermal stress. Data generated from the two groups were compared to identify significant difference in results caused by the thermal stressor, thus being stability indicating. 

Stability of PQ Grass (recommended storage conditions) on these methods show products remain in specification with expected analytical variation across the duration of the trial.

The forced degradation studies (extreme temperature) confirm that, for example, total antigenicity and MPL characterisation are stability indicating methods for PQ Grass. Assessment of these results allowed understanding of stability indicating methods for the product.

At recommend storage temperatures, allergoid products demonstrate robust stability over a period of up to and beyond 24 months. Furthermore, the proposed testing matrix is shown to be stability indicating based on the results of the FDS.