Skip to main content

PRAC confirms its previous conclusion on risk of inhibitor development with factor VIII medicines


No clear and consistent evidence exists of a difference in risk between plasma-derived and recombinant factor VIII medicines

Following a re-examination procedure, EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) has confirmed its previous conclusion of May 2017 that there is no clear and consistent evidence of a difference in the incidence of inhibitor development between the two classes of factor VIII medicines: those derived from plasma and those made by recombinant DNA technology.

Factor VIII is needed for blood to clot normally and is lacking in patients with haemophilia A. Factor VIII medicines replace the missing factor VIII and help control and prevent bleeding. However the body may develop inhibitors as a reaction to these medicines, particularly in patients starting treatment for the first time. This can block the medicines’ effect, so bleeding is no longer controlled.

Due to the different characteristics of individual products within the two classes, the PRAC reaffirmed that the risk of inhibitor development should be evaluated individually for each medicine, regardless of class. The risk for each product will continue to be assessed as more evidence becomes available.

To reflect the evidence currently available, the PRAC confirmed its recommendations that the prescribing information should be updated to include, as appropriate, inhibitor development as a very common side effect in previously untreated patients, and as an uncommon side effect in previously treated patients. The warning on inhibitor development should be amended to highlight that low levels of inhibitors pose less risk of severe bleeding than high levels.

The PRAC’s final recommendation will now be sent to EMA’s Committee for Medicinal Products for Human Use (CHMP) for the adoption of EMA’s opinion. Further details and information for patients and healthcare professionals will be published at that time.

More about the medicine

The review covers all medicines containing human factor VIII authorised in the European Union. Factor VIII is a clotting protein and these medicines are used to temporarily increase levels of this protein in patients with haemophilia A, helping to prevent and control bleeding.

Human plasma-derived factor VIII medicines are extracted from blood plasma. Recombinant factor VIII products, on the other hand, are produced by a method known as ‘recombinant DNA technology’: they are made by cells into which a gene (DNA) has been introduced to enable the cells to produce factor VIII.

Human factor VIII medicines include nationally authorised and centrally authorised products containing the active substances human coagulation factor VIII, efmoroctocog alfa, moroctocog alfa, octocog alfa, simoctocog alfa and turoctocog alfa.

More about the procedure

The review of factor VIII medicines was initiated on 7 July 2016 at the request of the German medicines authority Paul-Ehrlich-Institute, under Article 31 of Directive 2001/83/EC.

The review was carried out by the Pharmacovigilance Risk Assessment Committee (PRAC), the Committee responsible for the evaluation of safety issues for human medicines, which made a set of recommendations in May 2017.

Following a request from a company involved in the review, the PRAC re-examined its initial recommendation. The PRAC’s final recommendations will now be sent to the Committee for Medicinal Products for Human Use (CHMP), responsible for questions concerning medicines for human use, which will adopt the Agency’s opinion.

The final stage of the review procedure is the adoption by the European Commission of a legally binding decision applicable in all EU Member States.

Skip to main content Skip to the top of the page