A new era in immunotherapy and allergy diagnosis begins
The guideline titled "Allergen Products Development for Immunotherapy and Allergy Diagnosis in Moderate to Low Sized Study Populations" (Development of allergen-containing products for immunotherapy and allergy diagnosis in studies with medium to small participant numbers) was published by the European Medicines Agency (EMA) and comes into force on January 1, 2026. It was specifically created for allergy types with a limited number of patients. The significance, scope, and details of this guideline will be presented 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 a small number of patients
The difficulty of clinical research in certain allergy types is the starting point for this guideline. The main cause for the guideline is the difficulty in finding enough patients for studies on rare insect venom allergies or certain food allergies.
However, the EMA acknowledges that there may be alternative ways in such cases.
The allergenic products listed in the guidelines include:
- Affected organ system (e.g., upper and lower airways, eyes, skin, involvement of multiple organs (systemic reaction)),
- Allergen source (e.g., pollen, mites, animal hair, mold, insect venoms, food, chemicals),
- Allergen product (e.g., extracts, purified allergens, modified allergens, adsorbed allergens)
- regardless of the type of application (e.g., subcutaneous, sublingual, oral, percutaneous) Allergen products for allergen immunotherapy in Type I allergies and for the diagnosis of Type I and Type IV allergies
2. Legal basis and correct consulting strategy
When published, the sole application was considered insufficient. The assessment in conjunction with other EMA, CHMP, and ICH guidelines facilitates the achievement of results. For manufacturers and researchers, it is important to contact the regulatory authorities at an early stage of the work to clarify the development strategy.
The relevant guidelines are:
- Guideline for 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 the adjustment of starting doses 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: Estimation and Sensitivity Analyses in Clinical Trials – EMA/CHMP/ICH/436221/2017
- Guidelines for Selection of Control Group in Clinical Studies - CPMP/Ich/364/96 • Clinical Evaluation Guidelines - 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 medicinal products – information and data to be submitted in marketing authorization 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 included 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-immunotherapy - AIT (inhaled allergens, insect venom allergens, food allergens).
If standard laboratory tests or comprehensive non-clinical studies cannot be conducted in these categories, alternative methods such as literature research and expert opinions can be accepted. This approach is intended to help accelerate the development process in small populations.
4. Use of alternative data sources
In allergological studies with a small number of patients, retrospective data, case reports, and the use of products for "named patients" can be used as supporting data. The guideline emphasizes that alternative metrics such as PR (positivity rate) and RI (reaction index) play a role in assessing diagnostic accuracy.
With this EMA guideline, a new regulation for allergen product studies with a small number of patients is introduced. 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.
For detailed information, see the guidelines at: https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-allergen-products . -development-immunotherapy-allergy-diagnosis-moderate-lowsized-study-population_en.pdf