INTELLIGENCE OVERVIEW
Agency: EMA
The European Medicines Agency (EMA) has released Revision 2 of its guideline on the clinical investigation of human normal immunoglobulin for subcutaneous and/or intramuscular administration (SCIg/IMIg), adopted by CHMP on 16 March 2026. This updated guidance replaces the previous 2011 revision and provides clearer expectations for the development and regulatory evaluation of these plasma-derived products.
The revised guideline is particularly important for companies developing new SCIg/IMIg products or making significant manufacturing changes to already authorised products. It outlines the required evidence across biological data, pharmacokinetics, efficacy, safety, and special populations, helping ensure a harmonised approach to marketing authorisation submissions in the EU.
What’s New in Revision 2?
One of the most notable updates is the clarification of indication wording for secondary immunodeficiencies (SID). The guideline also now includes maintenance treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) as a recognised SCIg indication after stabilisation with IVIg. In addition, the document has been aligned, where relevant, with the revised EMA guidance for intravenous immunoglobulin (IVIg) products.
Key Clinical Development Expectations
For new SCIg/IMIg products, the guideline emphasises that biological and pharmacokinetic (PK) data are central to demonstrating activity and safety. In primary immunodeficiency (PID), applicants are expected to generate data from at least 40 patients, including a representative paediatric population, with monthly IgG trough level assessments over a defined study period.
For efficacy, the recommended approach remains a one-year, open-label, single-arm study in PID, with the rate of serious bacterial infections per patient per year as the primary endpoint. Secondary endpoints include infection burden, antibiotic use, hospitalisations, fever episodes, and time lost from work or school.
The guidance also confirms that, where efficacy has been established in PID, additional studies may not be required for SID, while CIDP maintenance therapy may be supported through a justified extrapolation based on PK, clinical, and literature data. For hepatitis A prophylaxis with IMIg, the guideline states that clinical data are not required, provided relevant pharmacopoeial standards are met.
Stronger Focus on Safety and Manufacturing Comparability
As expected for plasma-derived medicinal products, the revised guideline places strong emphasis on viral safety, transmissible agents, adverse event monitoring, and risk management planning. It also calls for specific assessment of local tolerability, paediatric safety, and any risks linked to excipients used in the formulation.
For already authorised products undergoing manufacturing process changes, EMA stresses the need to demonstrate comparability between pre-change and post-change product versions. Depending on the scale of the change, this may range from a focused PK study to a broader clinical data package.
KEYWORDS: Immunoglobulin, Clinical Development, safety requirements
REFERENCE: https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-clinical-investigation-human-normal-immunoglobulin-subcutaneous-or-intramuscular-administration-scig-imig-revision-2_en.pdf