A new era in immunotherapy and allergy diagnostics begins
The guideline, titled "Allergen Products Development for Immunotherapy and Allergy Diagnosis in Moderate to Low Sized Study Populations," was published by the European Medicines Agency (EMA) and will come into effect on January 1, 2026. It was specifically developed for allergy types with a limited number of patients. We will present the significance, scope, and details of this guideline in our blog post.
What innovations does this guideline bring, offering researchers and manufacturers flexible regulatory frameworks for the development of diagnostics and immunotherapy products? Here are the key points…
1. Flexible Approach for Allergy Types with Low Patient Numbers
The difficulty of clinical research for specific allergy types is the starting point for this guideline. The primary reason for the guideline is the challenge of recruiting sufficient patients for studies on rare insect venom allergies or certain food allergies.
However, the EMA acknowledges that alternative approaches may exist in such cases.
The allergenic products listed in the guidelines include:
- Affected organ system (e.g., upper and lower respiratory tract, eyes, skin, multi-organ involvement (systemic reaction)),
- Allergen source (e.g., pollen, mites, animal dander, molds, insect venoms, foods, chemicals),
- Allergen product (e.g., extracts, purified allergens, modified allergens, adsorbed allergens)
- Allergen products for allergen immunotherapy in Type I allergies and for the diagnosis of Type I and Type IV allergies, regardless of the route of administration (e.g., subcutaneous, sublingual, oral, percutaneous)
2. Legal Basis and Appropriate Consultation Strategy
Upon publication, the standalone application was deemed insufficient. Assessment in conjunction with other EMA, CHMP, and ICH guidelines facilitates the attainment of results. It is crucial for manufacturers and researchers to engage with regulatory authorities at an early stage of their work to clarify the development strategy.
The relevant guidelines are:
- Guideline on Clinical Trials in Small Populations – CHMP/EWP/83561/2005
- Guideline on Missing Data in Confirmatory Clinical Trials – EMA/CPMP/EWP/1776/99 Rev. 1
- Guideline on Adjustment for Baseline Covariates in Clinical Trials – EMA/CHMP/295050/2013
- Guideline on Statistical Principles for Clinical Trials – CPMP/ICH/363/96
- ICH E9 (R1) – Addendum to the Guideline on Statistical Principles for Clinical Trials: Estimands and Sensitivity Analysis in Clinical Trials – EMA/CHMP/ICH/436221/2017
- Guideline on the Choice of Control Group in Clinical Trials – CPMP/ICH/364/96 • Guideline on the Clinical Evaluation of Diagnostic Agents – CPMP/EWP/1119/98/Rev. 1
- Guideline on the Clinical Development of Specific Immunotherapy Products for the Treatment of Allergic Diseases – CHMP/EWP/18504/2006
- Guideline on Allergen Products: Guideline on Manufacturing and Quality Issues – EMEA/CHMP/BWP/304831/2007
- • Guideline on Process Validation for Finished Products – Information and Data to be Presented in Marketing Authorisation Applications – EMA/CHMP/CVMP/BWP/70278/2012-Rev1, Corr.1
- Recommendations for Common Regulatory Approaches for Allergenic Products – CMDh/399/2019
3. Flexibility in Quality and Non-Clinical Studies
The allergen categories contained in the guidelines are as follows.
- Allergens for diagnostic purposes in in vivo tests: Type I (prick test, provocation test, intradermal/intracutaneous test) and Type IV (epicutaneous patch test)
- Allergen Immunotherapies – AIT (inhalant allergens, insect venom allergens, food allergens).
If standard laboratory tests or comprehensive non-clinical studies cannot be conducted within these categories, according to the guideline, alternative methods such as literature reviews and expert opinions may be accepted. This approach aims to accelerate the development process in small populations.
4. Use of Alternative Data Sources
In allergology studies involving small patient cohorts, retrospective data, case reports, and the use of products for 'named patients' can be utilized as supportive data. The guideline emphasizes that alternative metrics such as PR (Positivity Rate) and RI (Reactivity Index) play a role in assessing diagnostic accuracy.
This EMA guideline introduces a new regulation for allergen product studies involving a small number of patients. Thanks to flexible data sources, alternative clinical designs, and adjustments in quality processes, the development of diagnostic and treatment options for rare allergy types is facilitated.
Detailed information can be found in the guidelines at: https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-allergen-products-development-immunotherapy-allergy-diagnosis-moderate-lowsized-study-populations_en.pdf