D2.223 - Using IgG antibodies to measure product potency for modified allergoid AIT

Grass allergen immunotherapy (AIT) products can be unmodified (native) or modified. Chemical modification is performed on grass pollens with the aim of reducing IgE reactivity while maintaining grass immunological relevance by IgG potency. Native pollen extracts are not structurally altered in any way therefore remain allergenic and capable of eliciting an IgE mediated immune response. 

PQ Grass 27600 SU is a broad-spectrum modified allergoid product which treats grass-pollen allergy while being hypoallergenic. The manufacturing process generates allergoids from a grass pollen extraction and associates them with a depot adjuvant system. European Pharmacopeia Guidelines on Allergen Products (01/2025: 1063) do not differentiate testing requirements for modified and unmodified products.  

Allergen profiles of native extracts were performed using western blotting with IgE human sera and IgG polyclonal antibodies. IgE reactivity is monitored throughout the stages of manufacture (beginning with native pollen extraction) to the drug product (DP) using specifically optimised ELISAs, using human sera, depending on modification status. IgG potency is quantified throughout the manufacturing process from drug substance (DS) to DP, using polyclonal ELISA.

Allergen profiles of the native extract using IgE and IgG antibodies show banding within the 24-35 kDa relevant allergen region, thus confirming that both antibody types are reactive at the native stage. The ELISA results show IgE reactivity declines to negligible levels once modified (DP). The IgG polyclonal ELISA demonstrates that the DP remains immunologically reactive with quantifiable IgG potency, enabling DP nominal potencies to be assigned.

Guidance for testing allergen products requires the IgE reactivity to be monitored from DS to DP. The challenge for a modified product is that this attribute provides negligible insight to product quality once modified. Whereas IgG binding capabilities remain regardless of native/allergoid status (throughout the manufacturing process), there is an argument that modified products should include IgG measurements for their potency assessment. This allows insight of product quality throughout the manufacturing process and reflects the therapeutic mode of action of the treatment.