RESUMO
BACKGROUND: The production of house dust mite (HDM) allergen products for allergy immunotherapy has traditionally been based on purified mite bodies or whole-mite culture, which are quite different source materials with a limited possibility for adjusting the chemical composition. The SQ HDM SLIT-tablet is a fast-dissolving pharmaceutical formulation that has been developed for sublingual immunotherapy (SLIT) of HDM respiratory allergic disease. OBJECTIVE: The objective of the present study was to establish a process for the production of drug substances for the SQ HDM SLIT-tablet offering a high reproducibility and independent control of the major allergens. METHODS: Process controls were documented in a comprehensive process parameter qualification. The analyses comprised composition by crossed immunoelectrophoresis, protein content by BCA, total IgE binding potency by Centaur assay, quantitative major allergen determination by radial immunodiffusion and ELISA, and the ranking of emPAI scores generated by mass spectrometry. RESULTS: Analysis of 20 batches of final product yielded a normalized mean and standard deviation for IgE binding potency of 100 ± 4.5. The standard deviation in the contents of Der f 1 and Der p 1 were correspondingly 11.9 and 6.1, whereas the variation in the group 2 major allergen content was 6.4. All measured 95% confidence limits between batches were less than 12%. CONCLUSIONS: The production process for the SQ HDM SLIT-tablet based on the separation of source material into four fractions each enriched in one major allergen enables precise adjustment of the relative major allergen content and high reproducibility of the final product.