Hydroxyethyl starch (HES) containing medicinal products - referral
Current status
Referral
Human
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 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.
If the suspension is confirmed by the European Commission, a direct healthcare professional communication (DHPC) will be sent to relevant healthcare professionals in due course, and published on a dedicated page on the EMA website.
HES solutions for infusion were authorised for the management of hypovolaemia (low blood volume) caused by acute blood loss where treatment with alternative infusion solutions known as ‘crystalloids’ alone is not considered to be sufficient.
HES solutions belong to a class of medicines known as colloids. Besides blood products, there are two types of medicines used for plasma volume replacement: crystalloids and colloids. Colloids contain large molecules such as starch, whereas crystalloids are solutions of low molecular weight substances and include saline and Ringer’s solutions.
In the EU, HES solutions for infusion were authorised via national procedures and are available in several Member States under various trade names.
EMA’s Pharmacovigilance Risk Assessment Committee (PRAC), responsible for the evaluation of safety issues for human medicines, issued its recommendation after reviewing the results of a drug utilisation study that was requested as part of additional risk minimisation measures resulting from an Article 107i referral procedure concluded in 2018.
The PRAC recommendation was sent to the Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh). The CMDh, also taking into consideration additional information from the marketing authorisation holders for HES solutions for infusion and external parties, endorsed the PRAC recommendation and adopted its position.
As the CMDh position was adopted by majority vote, it will now be sent to the European Commission, which will take an EU-wide legally binding decision in due course.
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.
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.
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:
Submissions must be accompanied by the submission form below, with all fields completed. The form must be used with Adobe Reader X+ or Adobe Acrobat X+:
Hydroxyethyl starch Article-107i referral - Stakeholder's submission form
Data submitted should make reference to the Pharmacovigilance Risk Assessment Committee (PRAC) questions:
Hydroxyethyl starch Article-107i referral - PRAC List of questions to be addressed by the stakeholders
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.
Personal data submitted are subject to data-protection rules as established by Regulation (EC) 45/2001.
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.
Description of documents published
Please note that some of the listed documents apply only to certain procedures.
Note that older documents may have different titles.