Chemistry, Manufacturing and Control

Standardized allergen preparations

Allergen extracts

Therapeutic and diagnostic allergen preparations are manufactured from standardised allergen extracts to ensure product consistency. The allergen extracts are made from natural raw materials. Standardization is obtained by controlling the quality of each batch of raw materials before use and by processing the extracts such that the content of relevant allergens as well as the allergenic activity is maintained within carefully chosen limits (i.e., product specifications). HAL Allergy uses advanced methodologies, such as antibody based assays or high-performance liquid chromatography, to identify and quantify the relevant allergens and to determine the allergenic activity of the extracts in order to ensure the quality of each allergen preparations.

Allergoids – for subcutaneous administration

HAL Allergy is a key leader in the manufacturing, standardization and characterization of allergoid preparations. Allergoids are widely used in subcutaneous specific allergy immunotherapy. An allergoid consists of an allergen extract that has been chemically modified to reduce its allergenic potential while remaining its immunological stimulus. This provides the opportunity to administer high doses of allergens with a reduced risk of side effects. Allergoids are generally obtained by polymerisation of the proteins in the allergen extracts using the cross-linking agent glutaraldehyde.

HAL Allergy applies state-of-the-art technologies to ensure the standardization and quality control of allergoid preparations. For example, mass spectrometry is used for the identification of the relevant allergens, size exclusion chromatography and lysine content for the determination of the degree of polymerisation and cross-linking, and fluorescence spectroscopy is applied to elucidate the protein structure after modification. In addition, biochemical antibody-based assays have been developed by HAL Allergy to measure the potency of allergoid preparations.

In the final product (PURETHAL®) the allergoid preparation is adsorbed to aluminium hydroxide. Aluminium hydroxide is the most commonly used and safe adjuvant for vaccine formulations. The presence of  relevant allergens, the protein structure, and the stability of the vaccine are important characteristics of the final product that are controlled at HAL Allergy. Mass spectrometry is used to identify the relevant allergens in the aluminium-adsorbed allergoid preparations. Antibody based assays, such as enzyme-linked immuno sorbent assays (ELISA), and physicochemical assays, such as circular dichroism and front-face fluorescence spectroscopy, are used to characterise the alum-adsorbed allergoid preparations, and to determine their stability.

Allergen drops – for sublingual administration

HAL Allergy also offers allergen drops (SUBLIVAC®) that can be administered by applying a few drops under the tongue (sublingual immunotherapy). SUBLIVAC® products are manufactured from standardised allergen extracts formulated in glycerol. Glycerol improves the dosing of the product by enhancing the stickiness in the mouth, and is a stabilizer of the allergen extracts.