Hydroxyethyl starch (HES) containing medicinal products

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Summary

 

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.

Information for patients
  • HES solutions for infusion are used to replace fluids in the body after acute (sudden) blood loss.
  • Because of the risk of kidney injury and death, HES solutions for infusion must not be used in patients with blood infection or kidneys problems or in critically ill patients.
  • If you are given a HES infusion, your doctor will monitor your kidneys to check that they are working well enough.
  • Patients who have questions or concerns should speak to their treating doctor.
Information for healthcare professionals
  • Because of the risk of kidney injury and mortality, HES solutions for infusion are contraindicated in patients with sepsis or in critically ill patients.
  • HES solutions for infusion should be used for managing hypovolaemia due to acute blood loss only when crystalloids alone are not considered sufficient. HES solutions should not be used for fluid maintenance.
  • Use of HES solutions for infusion should be restricted to the initial phase of volume resuscitation with a maximum time interval of 24 hours. Treatment should be guided by continuous haemodynamic monitoring so that the infusion is stopped as soon as haemodynamic goals have been achieved.
  • Additional studies are ongoing with HES solutions in patients with trauma and those undergoing elective surgery to further investigate the long-term safety of HES prescribed according to the recommendations for use (dose less than 30 ml/kg and duration less than 24 hours).
  • The expected benefit of treatment should be carefully weighed against the uncertainties with regard to long-term safety.
  • Alternative therapeutic options are available for routine clinical practice and should be considered according to relevant clinical guidelines.
  • HES solutions for infusion are contraindicated in patients with renal impairment or undergoing renal replacement therapy. The use of HES must be discontinued at the first sign of renal injury. An increased need for renal replacement therapy has been reported up to 90 days after HES administration. Patients’ kidney function should be monitored after HES administration.
  • HES solutions for infusion are contraindicated in severe coagulopathy. HES solutions should be discontinued at the first sign of coagulopathy. Blood coagulation parameters should be monitored carefully in case of prolonged use.
  • HES solutions for infusion are also contraindicated in dehydrated patients, hyperhydrated patients, patients with intracranial or cerebral haemorrhage, burn injuries, severe hyperkalaemia, hypernatraemia, hyperchloraemia, congestive heart failure, organ transplant patients and patients with impaired hepatic function.

Healthcare professionals will be informed in writing of the outcome of the review and the introduction of the new risk minimisation measures, which include the introduction of a controlled access programme requiring training of relevant healthcare professionals on the safe use of these medicines. This programme will be implemented by the companies holding the marketing authorisations. Further details about the training and the controlled access programme will be provided to hospitals and healthcare professionals in due time.

More about the medicine

HES solutions for infusion are used 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 sufficient. They are given by infusion (drip) into a vein and are used as blood volume expanders to prevent a dangerous drop in blood pressure following acute bleeding. They belong to the 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, such as saline or Ringer’s solutions, are electrolyte solutions.

In the European Union, HES solutions 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 solutions for infusion 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 was first conducted by the Pharmacovigilance Risk Assessment Committee (PRAC), EMA’s Committee responsible for the evaluation of safety issues for human medicines, which made a set of recommendations on 12 January 2018. The PRAC recommendations were sent to Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh), which adopted a position on 24 January 2018. The CMDh, a body representing EU Member States, is responsible for ensuring harmonised safety standards for medicines authorised via national procedures across the EU.

As the CMDh position was adopted by majority vote, it was sent to the European Commission. In April 2018, the European Commission requested that the PRAC and the CMDh further consider any possible unmet medical need that could result from a suspension, as well as the feasibility and likely effectiveness of additional risk minimisation measures.

After looking at these specific aspects, in May 2018 the PRAC confirmed its previous recommendation for suspension and sent a revised recommendation to the CMDh. The CMDh has now concluded that HES solutions for infusion should remain on the market provided that a combination of additional measures to protect patients is implemented.

As the CMDh position was adopted by majority vote, the CMDh position will now be sent back to the European Commission, which will take an EU-wide legally binding decision.

Name Language First published Last updated
Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) BG = bălgarski 2018-06-29 2018-08-07
Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) ES = español 2018-06-29 2018-08-07
Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) CS = čeština 2018-06-29 2018-08-07
Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) DA = dansk 2018-06-29 2018-08-07
Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) DE = Deutsch 2018-06-29 2018-08-07
Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) ET = eesti keel 2018-06-29 2018-08-07
Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) EL = elliniká 2018-06-29 2018-08-07
Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) EN = English 2018-06-29 2018-08-07
Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) FR = français 2018-06-29 2018-08-07
Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) IT = italiano 2018-06-29 2018-08-07
Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) LV = latviešu valoda 2018-06-29 2018-08-07
Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) LT = lietuvių kalba 2018-06-29 2018-08-07
Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) HU = magyar 2018-06-29 2018-08-07
Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) MT = Malti 2018-06-29 2018-08-07
Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) NL = Nederlands 2018-06-29 2018-08-07
Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) PL = polski 2018-06-29 2018-08-07
Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) PT = português 2018-06-29 2018-08-07
Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) RO = română 2018-06-29 2018-08-07
Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) SK = slovenčina 2018-06-29 2018-08-07
Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) SL = slovenščina 2018-06-29 2018-08-07
Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) FI = suomi 2018-06-29 2018-08-07
Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) SV = svenska 2018-06-29 2018-08-07
Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) HR = Hrvatski 2018-06-29 2018-08-07

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 statusEuropean Commission final decision
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
PRAC recommendation date12/01/2018
CHMP opinion/CMDh position date26/10/2017
EC decision date17/07/2018
OutcomeRisk 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 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

Under evaluation

Name Language First published Last updated
Hydroxyethyl starch Article-107i referral - Timetable for the procedure HR = Hrvatski 2017-10-27 2017-12-01

Recommendation provided by Pharmacovigilance Risk Assessment Committee

Name Language First published Last updated
Hydroxyethyl starch Article-107i referral - Summary of PRAC recommendation HR = Hrvatski 2018-01-12  

Position provided by CMDh

Name Language First published Last updated
Hydroxyethyl starch Article-107i referral - CMDh endorses PRAC recommendation HR = Hrvatski 2018-01-26 2018-02-02
Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) HR = Hrvatski 2018-06-29 2018-08-07
Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) HR = Hrvatski 2018-06-29 2018-08-07
Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) HR = Hrvatski 2018-06-29 2018-08-07
Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) HR = Hrvatski 2018-06-29 2018-08-07
Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) HR = Hrvatski 2018-06-29 2018-08-07
Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) HR = Hrvatski 2018-06-29 2018-08-07
Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) HR = Hrvatski 2018-06-29 2018-08-07
Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) HR = Hrvatski 2018-06-29 2018-08-07
Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) HR = Hrvatski 2018-06-29 2018-08-07
Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) HR = Hrvatski 2018-06-29 2018-08-07
Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) HR = Hrvatski 2018-06-29 2018-08-07
Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) HR = Hrvatski 2018-06-29 2018-08-07
Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) HR = Hrvatski 2018-06-29 2018-08-07
Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) HR = Hrvatski 2018-06-29 2018-08-07
Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) HR = Hrvatski 2018-06-29 2018-08-07
Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) HR = Hrvatski 2018-06-29 2018-08-07
Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) HR = Hrvatski 2018-06-29 2018-08-07
Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) HR = Hrvatski 2018-06-29 2018-08-07
Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) HR = Hrvatski 2018-06-29 2018-08-07
Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) HR = Hrvatski 2018-06-29 2018-08-07
Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) HR = Hrvatski 2018-06-29 2018-08-07
Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) HR = Hrvatski 2018-06-29 2018-08-07
Hydroxyethyl starch Article-107i referral - Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients (revised position) HR = Hrvatski 2018-06-29 2018-08-07

European Commission final decision

Name Language First published Last updated
Hydroxyethyl starch Article-107i referral - Annex III HR = Hrvatski 2018-06-29 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex III HR = Hrvatski 2018-06-29 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex III HR = Hrvatski 2018-06-29 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex III HR = Hrvatski 2018-06-29 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex III HR = Hrvatski 2018-06-29 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex III HR = Hrvatski 2018-06-29 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex III HR = Hrvatski 2018-06-29 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex III HR = Hrvatski 2018-06-29 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex III HR = Hrvatski 2018-06-29 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex III HR = Hrvatski 2018-06-29 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex III HR = Hrvatski 2018-06-29 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex III HR = Hrvatski 2018-06-29 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex III HR = Hrvatski 2018-06-29 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex III HR = Hrvatski 2018-06-29 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex III HR = Hrvatski 2018-06-29 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex III HR = Hrvatski 2018-06-29 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex III HR = Hrvatski 2018-06-29 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex III HR = Hrvatski 2018-06-29 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex III HR = Hrvatski 2018-06-29 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex III HR = Hrvatski 2018-06-29 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex III HR = Hrvatski 2018-06-29 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex III HR = Hrvatski 2018-06-29 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex III HR = Hrvatski 2018-06-29 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex III HR = Hrvatski 2018-06-29 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex III HR = Hrvatski 2018-06-29 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex I HR = Hrvatski 2017-10-27 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex I HR = Hrvatski 2017-10-27 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex I HR = Hrvatski 2017-10-27 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex I HR = Hrvatski 2017-10-27 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex I HR = Hrvatski 2017-10-27 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex I HR = Hrvatski 2017-10-27 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex I HR = Hrvatski 2017-10-27 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex I HR = Hrvatski 2017-10-27 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex I HR = Hrvatski 2017-10-27 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex I HR = Hrvatski 2017-10-27 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex I HR = Hrvatski 2017-10-27 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex I HR = Hrvatski 2017-10-27 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex I HR = Hrvatski 2017-10-27 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex I HR = Hrvatski 2017-10-27 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex I HR = Hrvatski 2017-10-27 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex I HR = Hrvatski 2017-10-27 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex I HR = Hrvatski 2017-10-27 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex I HR = Hrvatski 2017-10-27 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex I HR = Hrvatski 2017-10-27 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex I HR = Hrvatski 2017-10-27 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex I HR = Hrvatski 2017-10-27 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex I HR = Hrvatski 2017-10-27 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex I HR = Hrvatski 2017-10-27 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex I HR = Hrvatski 2017-10-27 2018-07-27
Hydroxyethyl starch Article-107i referral - Annex I HR = Hrvatski 2017-10-27 2018-07-27
Hydroxyethyl starch Article-107i referral - CMDh divergent positions HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Annex IV HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Annex IV HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Annex IV HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Annex IV HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Annex IV HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Annex IV HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Annex IV HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Annex IV HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Annex IV HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Annex IV HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Annex IV HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Annex IV HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Annex IV HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Annex IV HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Annex IV HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Annex IV HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Annex IV HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Annex IV HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Annex IV HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Annex IV HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Annex IV HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Annex IV HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Annex IV HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Assessment report HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Annex II HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Annex II HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Annex II HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Annex II HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Annex II HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Annex II HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Annex II HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Annex II HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Annex II HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Annex II HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Annex II HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Annex II HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Annex II HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Annex II HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Annex II HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Annex II HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Annex II HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Annex II HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Annex II HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Annex II HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Annex II HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Annex II HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Annex II HR = Hrvatski 2018-07-27  
Hydroxyethyl starch Article-107i referral - Annex II HR = Hrvatski 2018-07-27  

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:
European Commission final decision

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