On 4 September 2026 EMA announced that its safety committee, PRAC, has started a review of injectable iron-containing medicines over the risk of hypophosphataemia — low blood phosphate — and the bone problems that can follow it. The procedure is a textbook example of how a safety signal becomes an EU-wide referral, and of why the scope of such a review rarely stays where it started.
What triggered the review
Hypophosphataemia and hypophosphataemic osteomalacia are already known side effects of injectable iron medicines containing ferric carboxymaltose. Hypophosphataemia is listed in the product information as a common side effect, meaning it affects up to 1 in 10 people treated. The frequency of hypophosphataemic osteomalacia, by contrast, is recorded as unknown, because the available data do not support an estimate.
The product information already carries risk-minimisation measures, including recommendations to monitor blood phosphate in patients receiving high doses or long-term treatment and in those with known risk factors. The review was triggered by reports suggesting those measures are not working as intended:
- serious cases of hypophosphataemia, some resulting in osteomalacia, in people who had received only one or two doses;
- cases in patients with no recognised risk factors — the population the current measures are least designed to catch;
- delays in diagnosis, because symptoms such as tiredness, muscle pain and bone pain overlap with those of the iron deficiency being treated;
- bone changes such as osteomalacia that may not be visible on X-ray.
Why the scope is wider than the signal
The reports that prompted the procedure concerned ferric carboxymaltose. Similar cases have been reported with other injectable iron products, so EMA has drawn the scope around the whole class of parenteral iron-containing medicinal products rather than a single active substance. Oral iron medicines are excluded, on the basis that they deliver considerably lower amounts of iron over time and are therefore less likely to cause hypophosphataemia.
This is the pattern holders should expect. A referral is defined by the safety concern, not by the product that generated the reports. If your product shares the mechanism, you are likely in scope even if none of the triggering cases involved it.
What PRAC will actually decide
PRAC will assess the risk of hypophosphataemia and related bone disorders across injectable iron medicines, and — critically — the effectiveness of the existing risk-minimisation measures. It will then determine whether the risks affect the overall benefit-risk balance and whether changes to the marketing authorisations are needed.
That second limb matters. When a regulator reviews whether risk minimisation is working, the question is not only clinical. It is whether the warnings, monitoring recommendations and educational materials you put in place have changed prescriber and patient behaviour in practice. Holders who cannot evidence that are exposed.
The month in context
EMA publishes PRAC’s monthly workload, and the September 2026 figures put this single referral in perspective:
- 10 safety signals, 9 of them newly started
- 86 PSUR single assessments
- 73 risk management plans for centrally authorised medicines — 16 for new medicines, 57 for already authorised ones
- 25 post-authorisation safety studies: 17 protocols and 8 sets of results
- 1 referral started
Referrals are rare relative to routine pharmacovigilance. That is precisely why one lands hard when it arrives.
What holders of injectable iron products should be doing now
- Confirm whether your product falls within the published scope, and check the dedicated procedure page for the list of questions and the timetable.
- Assemble your cumulative review of hypophosphataemia and osteomalacia cases now, not when the list of questions arrives.
- Gather evidence on whether your existing risk-minimisation measures are effective — uptake of monitoring recommendations, prescriber awareness, any effectiveness studies.
- Brief your QPPV and make sure the PSMF reflects who is accountable for the response.
- Plan for the downstream work: if the outcome changes the product information, translations, artwork and national implementation follow.
How PQRA helps
We monitor PRAC and CHMP outputs for procedures that touch our clients’ portfolios, prepare cumulative safety reviews and rapporteur-ready response packages within procedural timelines, design and evaluate risk-minimisation measures so their effectiveness can actually be demonstrated, and manage product information updates and implementation with EOF in Greece.
If you hold an injectable iron product, or want a standing watch on referrals affecting your portfolio, speak to our pharmacovigilance team.
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