EMA PRAC Launches Class-Wide Review of Human Normal Immunoglobulins

Batch-specific hypersensitivity clusters across multiple human normal immunoglobulin products have prompted EMA's Pharmacovigilance Risk Assessment Committee (PRAC) to open a class-wide safety review, placing QA directors and regulatory affairs leads at manufacturers and marketing authorisation holders on immediate notice to prepare for data requests. The review spans all routes of administration, intravenous, subcutaneous, and intramuscular, meaning no product segment is outside scope.

Reported reactions range from rash and pruritus to anaphylaxis and angioedema, with clusters severe enough to trigger precautionary batch recalls in several EU Member States in recent months. Named products include Flebogamma DIF, Yimmugo, and Gamunex; the implicated batches have been withdrawn from market. Despite investigations already underway, root cause has not been established, and PRAC has confirmed it cannot yet determine whether the signal is confined to the recalled batches or extends across the broader product class.

For QA and post-market surveillance teams, the unresolved aetiology is the operative concern. PRAC will formally request all relevant data from marketing companies, meaning batch records, deviation logs, release testing data, and pharmacovigilance case narratives should be consolidated now. The review's class-wide framing suggests PRAC is not ruling out a manufacturing process variable, raw material sourcing, purification steps, or formulation excipients, as a contributing factor, though no such determination has been made publicly.

Hypersensitivity reactions are an acknowledged risk in existing product information for this class, with warnings already in place for serious reactions even in previously tolerant patients. The signal under review is not the existence of these reactions but their elevated frequency in association with specific batches, a distinction that will bear directly on how companies frame their CAPA documentation and signal assessment narratives when responding to PRAC's data requests.

Separately, PRAC has initiated a referral for Deanxit (flupentixol/melitracen), a fixed-dose combination indicated for depression and anxiety, following reports of serious neurological and psychiatric adverse events including movement disorders and cognitive disturbance, with some cases persisting after treatment discontinuation. That review proceeds under a standard referral procedure and is independent of the immunoglobulin signal.

The immunoglobulin review's outcome will determine whether additional risk minimisation measures are warranted across the class, with EMA committing to further communication as PRAC's assessment progresses.

Source: European Medicines Agency (EMA) via ema.europa.eu, 30 October 2026.