Factor VIII

  • Procedure started
  • Under evaluation
  • PRAC recommendation
  • CHMP opinion
  • European Commission final decision
Current status:
European Commission final decision


Factor VIII medicines: no clear and consistent evidence of difference in risk of inhibitor development between classes

EMA concludes review of human factor VIII medicines authorised in EU

The European Medicines Agency (EMA) has concluded 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.

EMA's review was started following publication of the SIPPET study (1), which concluded that recombinant factor VIII medicines had a higher incidence of inhibitor development than plasma-derived medicines. The review also covered other relevant interventional clinical trials and observational studies. When all these data were examined, they did not provide clear evidence of a difference in risk of inhibitor development between the two classes of medicines.

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 when patients first start treatment. The inhibitors reduce the medicines' effect, so bleeding is no longer controlled.

Due to the different characteristics of individual products within the two classes, EMA concluded 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 current knowledge, the prescribing information of factor VIII medicines will 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 will be amended to state that low levels of inhibitors pose less risk of severe bleeding than high levels.

Key facts

About this medicine
Approved name
Factor VIII
Associated names
  • Iblias
  • Elocta
  • Kovaltry
  • Nuwiq
  • Obizur
  • NovoEight
  • Voncento
  • ReFacto AF
  • Kogenate Bayer
  • Helixate NexGen
  • Advate
About this procedure
Current status
European Commission final decision
Reference number
Article 31 referrals

This type of referral is triggered when the interest of the Union is involved, following concerns relating to the quality, safety or efficacy of a medicine or a class of medicines.

Decision making model
Authorisation model
Centrally and nationally authorised products (mixed)
Key dates and outcomes
Procedure start date
PRAC recommendation date
CHMP opinion/CMDh position date
EC decision date
Risk minimisation measures

All documents

Procedure started

Recommendation provided by Pharmacovigilance Risk Assessment Committee

European Commission final decision

  • List item

    Factor VIII Article-31 referral - Assessment report (PDF/239.88 KB)


    First published: 05/12/2017
    Last updated: 05/12/2017

  • List item

    Factor VIII Article-31 referral - Annex II (PDF/113.63 KB)

    First published: 05/12/2017
    Last updated: 05/12/2017

  • List item

    Factor VIII Article-31 referral - No clear and consistent evidence of difference in risk of inhibitor development between classes (PDF/90.76 KB)


    First published: 15/09/2017
    Last updated: 05/12/2017

  • List item

    Factor VIII Article-31 referral - Annex III (PDF/77.63 KB)

    First published: 15/09/2017
    Last updated: 04/12/2017

  • List item

    Factor VIII Article-31 referral - Annex I (PDF/391.49 KB)

    First published: 08/07/2016
    Last updated: 05/12/2017

  • Description of documents published

    Please note that some of the listed documents apply only to certain procedures.

    • Overview - lay-language summary of the stage of the procedure
    • Notification – a letter from a Member State, the European Commission or the marketing authorisation holder requesting the initiation of the procedure
    • Scientific background – further background information from the triggering Member State on the issues leading to the initiation of the procedure (if applicable)
    • List of questions – questions agreed by the Committee requesting further information from the marketing authorisation holder(s) / applicant(s) to evaluate the issues identified
    • Timetable for the procedure – agreed timeframe to respond to the list of questions, to assess the issues and to adopt a conclusion
    • List of medicines concerned by the procedure – medicine(s) / active substance(s) concerned, and marketing authorisation holder(s) / applicant(s)
    • List of questions to be addressed by the stakeholders – call for data to be submitted by stakeholders (e.g. healthcare professionals, patient organisations, individual patients) (if applicable)
    • Stakeholder submission form – form to be used by stakeholders to submit data (if applicable)
    • Scientific conclusions – scientific conclusions of the PRAC and/or CHMP and/or CMDh
    • Assessment report – PRAC or CHMP assessment and conclusions on the issues investigated, including divergent positions (if applicable)
    • Divergent positions – divergent positions of the CHMP or CMDh members for pharmacovigilance procedures (if applicable)
    • Changes to the summary of product characteristics, labelling and package leaflet (amended sections or fully revised version) (if applicable)
    • Condition(s) to the marketing authorisation(s) – condition(s) for the safe and effective use of the medicine(s) (if applicable)
    • Condition for lifting the suspension – condition to be fulfilled for the suspension of the marketing authorisation(s) to be lifted (if applicable)
    • Timetable for implementation of CMDh position – agreed timeframe to submit and finalise the variation(s) implementing the outcome of the procedure (if applicable)

    Note that older documents may have different titles.


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