Hydroxyethyl starch (HES) containing medicinal products

  • Procedure started
  • Under evaluation
  • PRAC recommendation
  • CMDh position
  • European Commission final decision
Current status:
European Commission final decision

Overview

Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients

Medicines to remain on the market provided that training, controlled access and warnings on the packaging are implemented

The CMDh1 has decided that hydroxyethyl starch (HES) solutions for infusion should remain on the market provided that a combination of additional measures to protect patients is implemented. This follows further reflection, in consultation with EU Member States, on whether it would be feasible to introduce new measures that would effectively reduce the risks with these medicines.

HES solutions for infusion are used to replace plasma volume following acute (sudden) blood loss, where treatment with alternative products known as 'crystalloids' alone is not considered sufficient.

In January 2018, EMA's safety committee PRAC recommended suspending the marketing authorisations of these medicines because they continued to be used in critically ill patients and patients with sepsis despite restrictions introduced in 2013 due to the risk of kidney injury and death in these patients.

The CMDh agreed with the PRAC's assessment of the serious risks in critically ill patients and patients with sepsis. However, the CMDh gave further consideration to the place of HES in the clinical practice of some countries, noted that previous risk minimisation measures had some effect, and considered that a combination of new risk minimisation measures would effectively ensure that HES solutions are not used in patients at risk.

The new measures are:

  • the implementation of a controlled access programme by the companies holding the marketing authorisations to ensure that only accredited hospitals will be supplied with these medicines. The accreditation would require that relevant healthcare professionals receive training on the safe use of HES solutions for infusion. Further details about the training and the controlled access programme will be provided to hospitals and healthcare professionals in due time;
  • warnings in the medicines' packaging and at the top of the summaries of product characteristics (SmPCs) reminding healthcare professionals that these medicines must not be used in patients with sepsis or kidney impairment or in critically ill patients;
  • writing directly to healthcare professionals to ensure that they are fully aware of the conditions of use of the medicines and the groups of patients that must not receive them due to an increased risk of kidney injury and death.

The CMDh also requested marketing authorisation holders to conduct studies to check that only patients who should be treated with these medicines are receiving them. This is in addition to ongoing studies on the benefits and risks of HES solutions in patients with trauma and those undergoing elective surgery.

As the CMDh position was adopted by majority vote, the CMDh position was sent back to the European Commission, which took an EU-wide legally binding decision on 17 July 2018.


1The CMDh is a medicines regulatory body representing the European Union (EU) Member States, Iceland, Liechtenstein and Norway.

Key facts

About this medicine
Approved name
Hydroxyethyl starch (HES) containing medicinal products
International non-proprietary name (INN) or common name
hydroxyethyl starch (HES)
About this procedure
Current status
European Commission final decision
Reference number
EMEA/H/A-107i/1457
Type
Article 107i procedures

This type of procedure is triggered when a Member State or the European Commission consider that urgent action is necessary because of a safety issue. Situations that fall under this procedure include consideration for suspension or revocation of the marketing authorisation for a medicine, the prohibition of supply of a medicine or major changes to the marketing authorisation such as deletion of indications, reduction of the recommended dose or new contraindications. The procedure is also applicable in case of a safety issue with a class of medicines.

Decision making model
PRAC-CMDh
Authorisation model
Nationally authorised product(s)
Key dates and outcomes
Procedure start date
26/10/2017
PRAC recommendation date
12/01/2018
CHMP opinion/CMDh position date
26/10/2017
EC decision date
17/07/2018
Outcome
Risk minimisation measures

Data submission

The Agency invites all stakeholders (e.g. healthcare professionals, patients' organisations, the general public) to submit data relevant to this procedure. This is in accordance with Article 107j(1) of Directive 2001/83/EC.

The following requirements apply for data to be considered:

Submitting data

Send the completed form electronically to the stakeholders' submission inbox (public@ema.europa.eu). Specify the name of the medicine in the subject line of the e-mail.

The size of the submission file should not exceed 25 MB. If your attempt to send your data package to the dedicated e-mail address is unsuccessful, please use alternative submission means.

It is of the utmost importance that data are provided promptly, to avoid undermining the safety review. Due to the urgent nature of the procedure, you are strongly advised to submit your data in English.

Protection of personal data

Personal data submitted are subject to data-protection rules as established by Regulation (EC) 45/2001. They will be treated in accordance with the PDF iconspecific privacy statement for public consultations (EMA/310325/2012).

Treatment and publication of data

Data submitted will be received and recorded by the Agency.

The Agency will prepare a list of all submissions received, which will be published as an annex to the PRAC assessment report for transparency purposes and public awareness.

Please note that all data submitted in the context of this procedure may be shared and disclosed in the public domain.

All documents

Procedure started

Under evaluation

Recommendation provided by Pharmacovigilance Risk Assessment Committee

Position provided by CMDh

  • List item

    Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) (PDF/84.49 KB)


    First published: 29/06/2018
    Last updated: 07/08/2018
    EMA/422341/2018

  • List item

    Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) (PDF/84.49 KB)


    First published: 29/06/2018
    Last updated: 07/08/2018
    EMA/422341/2018

  • List item

    Hydroxyethyl starch Article-107i referral - CMDh endorses PRAC recommendation (PDF/80.63 KB)


    First published: 26/01/2018
    Last updated: 02/02/2018
    EMA/35795/2018

  • European Commission final decision

  • List item

    Hydroxyethyl starch Article-107i referral - Annex II (PDF/138.99 KB)


    First published: 27/07/2018
    Last updated: 27/07/2018

  • List item

    Hydroxyethyl starch Article-107i referral - Annex IV (PDF/41.9 KB)


    First published: 27/07/2018
    Last updated: 27/07/2018

  • List item

    Hydroxyethyl starch Article-107i referral - Assessment report (PDF/684.5 KB)

    Adopted

    First published: 27/07/2018
    Last updated: 27/07/2018
    EMA/171888/2018

  • List item

    Hydroxyethyl starch Article-107i referral - CMDh divergent positions (PDF/59.85 KB)


    First published: 27/07/2018
    Last updated: 27/07/2018

  • List item

    Hydroxyethyl starch Article-107i referral - Annex III (PDF/32.43 KB)


    First published: 29/06/2018
    Last updated: 27/07/2018

  • List item

    Hydroxyethyl starch Article-107i referral - Annex I (PDF/367.08 KB)


    First published: 27/10/2017
    Last updated: 27/07/2018

  • Document description

    • Annex I - List of the medicines affected by the referral
    • Annex II - Scientific conclusions of the CHMP or CMDh
    • Annex III - Changes to the summary of product characteristics, labelling or package leaflet - available when the CHMP or CMDh recommends changes to the product information. Also includes conditions for lifting of suspensions, if applicable
    • Annex IV - Conditions of the marketing authorisation - available when the CHMP or CMDh recommends other measures to be taken for the marketing authorisation such as safety measures or additional studies
    • Notification - A letter from a Member State, the European Commission or a marketing-authorisation holder requesting the initiation of a referral procedure
    • Rationale for triggering - Background provided by the party triggering the referral explaining the issues leading to the initiation of the procedure
    • PRAC list of questions - Questions agreed by the PRAC requesting further information to evaluate the issues identified
    • PRAC timetable - Timeframe agreed by the PRAC to receive information, assess the issues and adopt a recommendation
    • PRAC / CHMP or CMDh assessment report - The assessment and conclusions of the PRAC and CHMP or CMDh on the issues investigated

    News

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