Laboratory of Immunobiochemistry, Division of Bacterial, Parasitic, and Allergenic Products, Office of Vaccine Research and Review, CBER/FDA, Silver Spring, MD, USA.
Division of Allergology, Paul-Ehrlich-Institut, Langen, Germany.
Clin Exp Allergy. 2017 May;47(5):604-617. doi: 10.1111/cea.12931.
In the United States, the Center for Biologics Evaluation and Research of the US Food and Drug Administration regulates biologics used for diagnosis and treatment of allergic diseases. The Code of Federal Regulations 21CFR680.3(e) states that when measured, the potency of an allergenic extract is assessed according to its allergenic activity. As of 2016, 19 allergenic extracts are standardized for potency in the United States. While these standardized extracts constitute a minority of those available, they treat the most prevalent allergies (e.g. grass and ragweed pollens, dust mites, and cat) and those that induce life-threatening anaphylaxis (e.g. Hymenoptera venom). Standardization for potency enhances safety and efficacy of immunotherapy by minimizing the risks of variations in allergen dosing when switching from one lot of manufactured extract to another, and by providing an objective measure of stability of each lot of allergenic extract over time. Allergenic extracts that have multiple immunodominant allergenic proteins are standardized with little or no information about compositional differences among extracts. Here, we propose application of mass spectrometry towards measurement of compositional differences among extracts that may affect the efficacy and safety of allergen immunotherapy. In addition, we discuss of house dust mite allergen extracts as a prototypical complex extract that may be standardized by mass spectrometry.
在美国，美国食品和药物管理局的生物制品评估和研究中心负责监管用于诊断和治疗过敏性疾病的生物制品。联邦法规 21CFR680.3(e)规定，当进行测量时，根据变应原提取物的变应原活性来评估其效价。截至 2016 年，美国有 19 种变应原提取物的效价标准化。虽然这些标准化提取物构成了可用提取物的少数，但它们治疗最常见的过敏症（例如草和豚草花粉、尘螨和猫）和那些引起危及生命的过敏反应（例如膜翅目毒液）。通过最小化从一批生产的提取物切换到另一批提取物时变应原剂量的变化风险，并提供每个变应原提取物随时间稳定的客观测量，效价标准化增强了免疫疗法的安全性和有效性。具有多种免疫优势变应原蛋白的变应原提取物的标准化几乎没有或没有关于提取物之间成分差异的信息。在这里，我们提出将质谱应用于测量可能影响变应原免疫疗法疗效和安全性的提取物之间的成分差异。此外，我们还讨论了屋尘螨变应原提取物作为可能通过质谱标准化的典型复杂提取物。
