EMA Guidance: Core SmPC Guideline for Subcutaneous and Intramuscular Immunoglobulins: What Manufacturers Need to Know

Human normal immunoglobulin (IgG) products administered via the subcutaneous (SCIg) or intramuscular (IMIg) route are essential therapeutic options for managing a wide spectrum of immune-related conditions. To support harmonisation and clarity across the European Union, the European Medicines Agency (EMA) has released a revised draft of the “Guideline on Core Summary of Product Characteristics (SmPC) for Human Normal Immunoglobulin for Subcutaneous and Intramuscular Administration” in December 2024. This document provides detailed recommendations for marketing authorisation holders (MAHs) on how to structure and standardise product information for SCIg and IMIg formulations.

The purpose of this SmPC guideline is to ensure a harmonised, evidence-based approach for drafting product characteristics of plasma-derived immunoglobulin products intended for subcutaneous or intramuscular administration. It applies to both new marketing authorisations and variation applications.

The guideline reflects updates in clinical understanding and regulatory harmonisation, notably incorporating use in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and aligning with IVIg guidance. The scope excludes fragmented or chemically modified IgG products and focuses strictly on those complying with the European Pharmacopoeia monographs for human normal immunoglobulin.

SCIg products are recommended for:

• Replacement therapy in primary and secondary immunodeficiencies

• Maintenance therapy in CIDP, after IVIg initiation

IMIg products are indicated for hepatitis A prophylaxis, covering both pre- and post-exposure in adults and children.

Paediatric use should be clearly supported by clinical data where applicable.

Dosing recommendations include:

• PID: 0.4–0.8 g/kg/month

• SID: 0.2–0.4 g/kg/month

• CIDP: Weekly SCIg (0.2–0.4 g/kg)

• Hepatitis A (IMIg): 0.17 mL/kg

SCIg administration requires patient training, while IMIg must be administered by healthcare professionals.

Immunoglobulin is contraindicated in patients with hypersensitivity, IgA deficiency with anti-IgA antibodies, or severe thrombocytopenia (for IM use). Close monitoring is advised during initial doses, especially in high-risk populations or when switching products. Live vaccines may be less effective after immunoglobulin use. The guideline recommends delaying vaccinations like measles, mumps, rubella, and varicella for up to 3 months, and even longer in the case of measles.

The most commonly reported side effects with SCIg are local injection site reactions, such as swelling, redness, and itching. Systemic side effects may include fever, headache, nausea, or hypotension. Serious adverse events are rare but include anaphylaxis, aseptic meningitis, and thromboembolic complications.

There is no known toxicity from overdose; however, excessively high doses may lead to increased blood viscosity, particularly in high-risk populations such as the elderly or patients with renal disease.

The guideline concludes with essential information for the pharmaceutical section of the SmPC. This includes:

• A list of excipients and storage instructions

• Details about shelf life, container type, and pack size

• Instructions on visual inspection before use and disposal practices

Manufacturers are also reminded of the importance of batch traceability and recording product codes and expiration dates.

For MAHs preparing dossiers for new approvals or updating existing products, aligning with this SmPC guidance is an essential step in achieving regulatory success.

Download the full guidance document (PDF):👉 EMA SCIg/IMIg SmPC Guidance