868:
High consistency in allergen composition of SQ house dust mite (HDM) tablet for sublingual immunotherapy (SLIT)
Monday, March 5, 2018
South Hall A2 (Convention Center)
Helene Henmar, MSc, Andrew Mikles, Karin Grosch, Jorgen N. Larsen, PhD
RATIONALE:

HDM immunotherapy products have traditionally been based on purified mite bodies or whole mite culture with little or no possibility for adjusting the allergen composition. For the SQ-HDM SLIT-tablet high consistency was achieved in a fractionation process.

METHODS:

The two most important HDM species causing respiratory allergic disease, Dermatophagoides farinae and pteronyssinus, were grown separately under controlled conditions. After termination the cultures were separated using an automated mechanical sieve. The fraction containing the smallest particles predominantly contained faecal particles rich in group 1 major allergen, whereas an intermediate fraction contained predominantly mite bodies rich in group 2 major allergen.

Fractions were mixed 1:1 based on μg major allergen forming one drug substance (DS) for each mite species. Quality control included total IgE binding capacity by Centaur assay, major allergen determination by radial immuno diffusion; protein and antigen profile by SDS-PAGE and crossed immunoelectrophoresis, respectively.

RESULTS:

Data were normalized relative to the mean, and the standard deviation of Derf1 in DS was 11.7% (14.7% and 17.7% in source material, SM) and for Derp2 12.3% (12.1% and 16.7% in SM), respectively. The corresponding figure for Derp1 was 9.0% (12.7% and 16.8% in SM) and for Derp2 9.9% (17.8% and 15.8% in SM).

The analyses of the DS showed that fractionation resulted in a consistent DS without compromising the complexity in the protein and antigen profiles.

CONCLUSIONS:

Variation in allergen content was observed in the source material, but fractionation enabled a process resulting in a highly standardised composition of the SQ-HDM SLIT-tablet.