541:
Consistent composition and potency of freeze dried tablets for sublingual immunotherapy
Sunday, March 4, 2018
South Hall A2 (Convention Center)
Helene Henmar, MSc, Susanne Sønderkær, Pernille H Nørby, Lars H Christensen, PhD, Jorgen N. Larsen, PhD
RATIONALE:

Consistency in composition and potency of allergen products is important for the clinical performance in everyday practise. Release kinetics of individual allergen components from source materials differ, and the production process must be optimised individually for every source material in order to secure consistent composition and potency of the final drug product.

METHODS:

Aqueous extraction of grass and ragweed pollen as well as house dust mite (HDM) particles was performed under chemical conditions resembling the conditions on the airway mucosa. Tablet disintegration experiments were performed in water. 69, 29 and 35 batches were analysed from grass, ragweed and HDM SLIT-tablets, respectively. Release kinetics were assessed by immunoelectrophoresis (IE), immunodiffusion, IgE binding, ELISA and mass spectrometry.

RESULTS:

Release kinetics from source material vary among allergen molecules and complete release can take up to two hours. Major allergen content released from tablets was normalized relative to the mean and the standard deviation (SD) measured was 5.0% for Phl p 5, 6.6% for Amb a 1 and 9.8%, 6.7% and 11.4% for Der f 1, Der p 1 and Der 2, respectively. The SD of IgE-binding potency was 6.2%, 8.4% and 5.5% for grass, ragweed and HDM tablets, respectively. All relevant allergens were assessed semi-quantitatively by IE ensuring optimal complexity of the final products. Disintegration time for all 3 freeze dried tablet formulations was within 2 sec.

CONCLUSIONS:

The SLIT-tablets contain a consistent composition and potency, which is achieved in an optimised production process taking into account the variable kinetics of extration of individual allergen components.