Introduction:
Allergen extracts are biological products used to diagnose and treat allergic diseases. Allergy diagnosis is performed by a careful review of the patient’s medical history, often followed by in vivo and/or in vitro testing, which involve the use of allergen extracts. Allergen avoidance should be the first measure to prevent allergies. However, this approximation is not always possible to implement, and it is not always effective.
Immunotherapy can modulate the immune system and prevent allergies. Medication, is the third alternative to manage allergies because is expensive and does not prevent the immune reaction responsible for allergies. However, medication can relieve allergy symptoms.
Various steps are involved in the production of allergen extracts. These steps include, but are not limited to, the proper selection and procurement of allergenic raw materials, the manufacturing procedures utilized, the quality measures in place to assure that the extracts have a consistent allergen composition and potency, and the measures in use to guarantee a particular shelf-life and expiration date.
The allergens utilized in allergen extracts can be classified as natural or recombinant. The associated materials to produce them are manufactured differently.
Natural allergens have been used for many years in allergen extracts and will continue to be used for the time to come because of the varying limitations regarding the production and use of recombinant allergens. For example, it is currently not possible to obtain recombinant forms of all clinically relevant allergens. In addition, the safety and efficacy of such allergens need to be properly documented through appropriate clinical trials, which takes time and is extremely expensive.
Most catalogs of allergen extracts list pollen, mites, fungi (molds), insects, epithelia (mammalian allergens), hymenoptera venoms, foods, and “others”. Therefore, the procurement of the raw materials to produce those allergen extracts varies, depending on the product.
Natural allergenic raw materials are diverse in origin and have different characteristics. They are obtained from the outdoor environment (i.e. pollen), from laboratory cultures (i.e mites and fungi), animal groomers (i.e. epithelia), or supermarkets (foods).
This is the first post of a series associated with the topic of the production of allergen extracts. In this post, we provide a brief description of the manufacturing steps associated with the manufacturing of extracts. Subsequently, we will address the complex topics of the natural allergenic materials used in the production of allergen extracts as well as their stability and expiration dates.
Steps involved in the production of allergen extracts:
A number of steps are involved in the production of allergen extracts. These steps vary depending on the types of extracts and their intended purpose/s. For example, allergen extracts for in vitro diagnosis are not subjected to the same rigorous quality measures as those for in vivo use. However, a general, overview of the steps involved in the production of allergen extracts is provided below.
Step #1: Once raw materials are received at allergen manufacturing companies, batch records are initiated, and the materials are placed on quarantine. Subsequently, the identity and purity of the raw materials are determined by macroscopic and/or microscopic inspection or by chemical/immunochemical testing.
Step #2: Moisture content in the materials is measured. Subsequently, the materials should be dried, if necessary, to prevent potential microbial growth and product bio-deterioration. Then, raw materials are released and stored until further processing. Ideally, raw materials should be stored frozen to preserve their stability and shelf-life over a given period, as indicated by an expiration date.
Allergen manufacturing companies should have real-time stability protocols in place for different raw material types, according to accepted guidelines. The information derived from the completion of those studies would likely identify selective expiration dates for different raw materials, as expected due to the intrinsic nature of their allergens.
Step #3: Raw materials are processed to various levels before extraction. The materials are typically washed and defatted with a solvent. Subsequently, they are sieved, milled, and/or powdered, as appropriate.
After raw materials are processed, they are known as “source materials”, which are the products that will be extracted to produce intermediate and/or final extracts. Source materials should also be placed on stability programs.
Step #4: After source materials are extracted, the resulting extracts are clarified, dialyzed, sterile-filtered, mixed with a stabilizing agent (i.e., glycerin), and stored. Allergen extracts are often lyophilized to preserve their integrity. Lyophilized extracts are common intermediate products used for further manufacturing.
Additional activities the Allergen Science & Consulting has been and is performing regarding the production of allergen extracts:
Because pollen is a challenging allergenic material, we have published a paper that exclusively addresses the production of pollen extracts. Please contact us if you would like to receive a copy of this article.
Allergen Science & Consulting leaded the preparation and review of a series of articles, entitled “How Allergen Extracts Are Made”, which addresses each type of product individually. We selected renowned scientists from different countries to contribute to the articles, which were published in the Annals of Allergy and Immunology. Please contact us if you have any inquiries about their content.