Vivaglobin - referral

Current status

European Commission final decision

Overview

The European Medicines Agency (EMA) has completed a review of Vivaglobin, following the detection of impurities in the medicine which could cause thromboembolic events (problems due to formation of blood clots in blood vessels). The Agency's Committee for Medicinal Products for Human Use (CHMP) has recommended changes to the manufacturing process to prevent the presence of these impurities and thus reduce the risk of thromboembolic events.

What is Vivaglobin?

Vivaglobin is a solution for injection under the skin that contains human normal immunoglobulin extracted from blood as the active substance. Human normal immunoglobulins are antibodies (types of protein) normally found in the blood that help the body to fight infections and other diseases.

Vivaglobin is used to provide antibodies to adults and children with primary immunodeficiency syndromes (people who are born with abnormally low levels of antibodies). It is also used to provide antibodies to cancer patients who lack them.

Vivaglobin is authorised in the European Union (EU) under a mutual recognition procedure and is available in the following EU Member States: Austria, Belgium, Denmark, Finland, France, Germany, Greece, Hungary, Italy, Luxembourg, the Netherlands, Poland, Portugal, Spain, Sweden, as well as Norway.

Why was Vivaglobin reviewed?

On 10 March 2011, the German medicines regulatory agency informed the EMA of a few cases of thromboembolic events, including strokes and pulmonary embolism (clot in a blood vessel supplying the lungs), in patients receiving the medicine. Although thromboembolic events are known to occur with immunoglobulins given by injection into a vein, they had not previously been linked with immunoglobulins given by injection under the skin.

Investigations by the company found that some of the materials used during the extraction of Vivaglobin from human blood produced impurities capable of triggering the formation of blood clots. Therefore, the company took corrective action to remove these impurities by modifying the manufacturing process. This modification of the manufacturing process was in line with the approved marketing authorisation.

On 17 March 2011, the German medicines regulatory agency decided to refer the matter to the CHMP so that the Committee could conduct an EU review of the root cause of the problem and evaluate the measures introduced in order to issue an opinion on whether the marketing authorisation of Vivaglobin should be maintained, varied, suspended or withdrawn.

What are the conclusions of the CHMP?

Based on evaluation of the root cause of the problems that occurred during the manufacture of Vivaglobin, the CHMP concluded that the changes to the manufacturing process effectively reduce the risk of thromboembolic events. Therefore, the Committee recommended that the changes in the manufacturing process should be formally included in the marketing authorisation of Vivaglobin.

A European Commission decision on this opinion will be issued in due course.

Questions and answers on the review of Vivaglobin (human normal immunoglobulin, solution for injection under the skin)

Reference Number: EMA/107736/2012Summary:

The European Medicines Agency (EMA) has completed a review of Vivaglobin, following the detection of impurities in the medicine which could cause thromboembolic events (problems due to formation of blood clots in blood vessels).

Key facts

About this medicine

• Approved name:
  Vivaglobin
• International non-proprietary name (INN) or common name:
  human normal immunoglobulin
• Class:
  -

About this procedure

• Current status:
  European Commission final decision
• Reference number:
  EMEA/H/A-36/1296
• Type:
  Article 36 referrals (prior to July 2012)

  This type of referral applied for a marketing authorisation that were granted via the mutual-recognition or decentralised procedure. It was triggered when a Member State considered that action (variation, suspension or withdrawal) was needed on the grounds of the need to protect public health. This referral has been replaced by Articles 107i and 31.

Key dates and outcomes

• CHMP opinion date:
  16/02/2012
• EC decision date:
  07/05/2012

All documents

Questions and answers on the review of Vivaglobin (human normal immunoglobulin, solution for injection under the skin)

Reference Number: EMA/107736/2012Summary:

The European Medicines Agency (EMA) has completed a review of Vivaglobin, following the detection of impurities in the medicine which could cause thromboembolic events (problems due to formation of blood clots in blood vessels).

European Commission final decision

Vivaglobin Article-36 referral - Assessment report

AdoptedReference Number: EMA/289571/2012

Vivaglobin Article-36 referral - Annex I

Vivaglobin Article-36 referral - Annex II

Vivaglobin Article-36 referral - Annex III

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.