Hydroxyethyl starch (HES) containing medicinal products

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Summary


EMA starts new review of hydroxyethyl-starch containing medicines

Studies show low adherence to restrictions aimed at reducing risks of kidney injury and death

The European Medicines Agency (EMA) has started a new review of medicines containing hydroxyethyl-starch (HES). These products are used for the management of hypovolaemia (low blood volume) caused by acute (sudden) blood loss, where treatment with alternative infusion solutions known as ‘crystalloids’ alone is not considered to be sufficient. HES medicines are given by infusion (drip) into a vein and are used as blood volume expanders to prevent shock following acute bleeding.

The review is triggered by results from two drug utilisation studies indicating that HES-containing medicines were being used outside their authorised uses, including in critically ill patients and those with sepsis and kidney injury despite restrictions introduced in 2013 to reduce the risks of kidney problems and deaths.

The drug utilisation studies had been requested by EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) in 2013 as a condition to the marketing authorisations of these products, in order to verify adherence to the new restrictions.

The PRAC will review the results of these studies, and all other available data, and their impact on the benefit-risk balance of HES-containing medicines for infusion and issue a recommendation on whether their marketing authorisations should be maintained, varied, suspended or withdrawn across the EU.

The Agency invites all stakeholders (e.g. healthcare professionals, patients’ organisations, and the general public) to submit data relevant to this procedure. Full details are available under the ‘data submission’ tab.

More about the medicines

Infusion solutions containing HES are indicated for volume replacement and belong to the class of medicines known as colloids. There are two main types of medicines used for volume replacement: crystalloids and colloids. Colloids contain large molecules such as starch, whereas crystalloids, such as saline or Ringer’s solutions, contain smaller molecules.

In the European Union, HES-containing medicines for infusion have been approved via national procedures and are available in the Member States under various trade names.

More about the procedure

The review of HES-containing medicines was initiated on 17 October 2017 at the request of the Swedish Medical Products Agency, under Article 107i of Directive 2001/83/EC.

The review is being carried out by the Pharmacovigilance Risk Assessment Committee (PRAC), the Committee responsible for the evaluation of safety issues for human medicines, which will make a set of recommendations. As HES-containing medicines are all authorised nationally, the PRAC recommendation will be forwarded to the Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh), which will adopt a position. The CMDh is a body representing EU Member States as well as Iceland, Liechtenstein and Norway. It is responsible for ensuring harmonised safety standards for medicines authorised via national procedures across the EU.

Name Language First published Last updated
Hydroxyethyl starch Article-107i referral - Review started (English only) 2017-10-27  

Key facts

About this medicine

Approved nameHydroxyethyl starch (HES) containing medicinal products
International non-proprietary name (INN) or common name

hydroxyethyl starch (HES)

Associated names
Class

About this procedure

Current statusProcedure started
Reference numberEMEA/H/A-107i/1457
TypeArticle 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 modelPRAC-CMDh
Authorisation modelNationally authorised product(s)

Key dates and outcomes

Procedure start date26/10/2017

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 specific 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

Document description:

  • Annex I - List of the medicines affected by the referral
  • Annex II - Scientific conclusions of the Committee for Medicinal Products for Human Use (CHMP) or Coordination Group for Mutual Recognition and Decentralised Procedures - Human (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 / CMDh assessment report - The assessment and conclusions of the PRAC and CHMP or CMDh on the issues investigated

Current status:
Procedure started