European Medicines Agency Agrees on Action Plan Following the Recall of Viracept and Recommends Suspension of the Marketing Authorisation
LONDON, June 21, 2007-The European Medicines Agency today agreed on an action plan to follow-up patients who were exposed to contaminated Viracept (nelfinavir). Viracept, from Roche Registration Limited, is an antiretroviral medicine used to treat HIV-1 infected adults, adolescents and children of 3 years of age and older. It was recalled from the European market in early June 2007 because during the manufacturing process some batches had become contaminated with ethyl mesilate, a known genotoxic substance (harmful to DNA).
A meeting of toxicology experts held at the EMEA on 13 June 2007 concluded that there are currently insufficient data to establish which doses of ethyl mesilate may be toxic in humans. The CHMP has therefore requested the company to carry out studies in animals in order to calculate toxic levels of ethyl mesilate more precisely. Preliminary results from these studies should be available by the end of this year.
While awaiting the above results, the Agency’s Committee for Medicinal Products for Human Use (CHMP) has asked the company to identify the group of patients who have been exposed to contaminated batches of Viracept, with a view to establishing appropriate follow-up and monitoring. The current view of the CHMP is to follow patients exposed to high levels of contaminant in the batches of Viracept released since March 2007, all pregnant women who have ever been exposed to Viracept and all children who have ever been exposed to Viracept, including those exposed in utero. The situation will be reviewed as data become available.
Furthermore, the European Medicines Agency today recommended to the European Commission to suspend the marketing authorisation for Viracept (nelfinavir), because it had concerns that the quality and therefore the safety of Viracept could not be ensured at this time. As a consequence of the recommended suspension, Viracept will continue to be unavailable for patients until corrective measures have been implemented to resolve the manufacturing issues identified by the CHMP.
Further updates will be provided as more information becomes available.
- 1. The CHMP reviewed the marketing authorisation of Viracept on the request of the European Commission under Article 20 of Regulation (EC) No 726/2004. This type of procedure is initiated in cases where there are public health concerns with a centrally authorised medicine.
- 2. The recall was initiated on 6 June 2007. It affected the 27 EU Member States and Iceland, Liechtenstein and Norway. A press release was published and can be found here.
- 3. Viracept had been authorised as an oral powder 50 mg/g, 250 mg tablets and 250 mg film-coated tablets. The marketing authorisation holder is Roche Registration Limited. More information can be found in the European Public Assessment Report for Viracept: http://www.emea.europa.eu/humandocs/Humans/EPAR/viracept/viracept.htm.
- 4. The suspension of a marketing authorisation is a precautionary measure, during which time a medicinal product is not available. The lifting of the suspension is conditional on the marketing authorisation holder resolving the issues identified by the Agency.
- 5. A question and answer document has been prepared and can be found here.
- 6. This press release, together with other information about the work of the EMEA, can be found on the EMEA website: http://www.emea.europa.eu
Media enquiries only to:
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QUESTIONS AND ANSWERS ON THE FOLLOW-UP TO THE VIRACEPT RECALL1
The European Medicines Agency (EMEA) and the European Commission have now taken further steps following the recall of Viracept by Roche Registration Limited, because of a contamination with a harmful substance. Patients who may have been exposed will be closely monitored while more information on the harmful potential of the contaminant is gathered. The EMEA has recommended to the European Commission that Viracept’s marketing authorisation be suspended.
What is Viracept?
Viracept is an antiviral medicine used in combination with other antiviral medicines to treat adults, adolescents and children over 3 years of age who are infected with human immunodeficiency virus (HIV-1), the virus that causes acquired immune deficiency syndrome (AIDS). Viracept contains nelfinavir mesilate.
What has been happening with Viracept?
Recent batches of nelfinavir mesilate have been contaminated with high level of ethyl mesilate, a known genotoxic substance (harmful to DNA, the genetic material in cells). The medicine has been recalled and all packs are being returned to the manufacturer.
What is the level of risk for patients?
Genotoxic substances such as ethyl mesilate may increase the risk of developing cancer. Is it difficult at present to assess the risk to patients because there are insufficient data to establish which doses of ethyl mesilate may be toxic in humans.
What are the consequences for patients?
Patients who were receiving Viracept should have been ‘switched’ by their doctors to another anti-HIV medication.
Patients who have been taking Viracept may have been exposed to ethyl mesilate, and the EMEA has requested the company to establish ways to follow them up. Patients who will be closely followed and monitored are all those who have been exposed to the medicine made from highly contaminated batches, as well as women who took the medicine during pregnancy and children who have taken Viracept at any time or were exposed to it in the womb.
How will patients know if they have been exposed?
The level of exposure to ethyl mesilate will depend on the level of contamination in the Viracept they have taken. When looking into the contamination, the company have already found out that the higher level of contamination was seen in the batches of Viracept that have been released on the market since March 2007. However, they have also looked at earlier batches, and found that some contamination, but at lower levels, had also happened in the past. At the moment, the company is actively identifying which batches were affected, so that, in each country, patients who have taken potentially contaminated Viracept can be traced, identified and followed up.
1 The previous question and answer document on the recall of Viracept was published on 6 June 2007, and can be found here.
2 This was carried out as a review procedure under Article 20 of Regulation (EC) 726/2004 initiated by the European Commission.
3 This is set at 0.6 parts per million (ppm).
What is happening now?
The CHMP has recommended that the marketing authorisation for Viracept be suspended2, because it has concerns that the quality and therefore the safety of the medicine cannot be guaranteed at present. The Committee’s opinion has now been forwarded to the European Commission in order to issue a Decision.
What is going to happen in the next few months?
A group of experts met at the EMEA on 13 June 2007 to look at the information available on the toxicity of ethyl mesilate. They have now requested that the company carry out specific animal studies with ethyl mesilate, with the aim of identifying more precisely what level of exposure is harmful. The protocols for the studies, which describe how they will be carried out, will be checked by the CHMP before the studies start, to ensure that they are adequate for their purpose. Preliminary results will be available by the end of the year.
Until then, the CHMP has proposed that a level for ethyl mesilate in nelfinavir mesilate be set, in line with currently available animal study results and scientific consensus on genotoxic impurities3. In practice, this would correspond to a maximum daily intake of around one and a half micrograms of ethyl mesilate for an adult patient taking the recommended daily dose of Viracept.
The EMEA is also working with Roche to put in place a full Risk Management Plan, a set of measures to ensure that the risk associated with contaminated Viracept is handled in an appropriate manner. In addition to finding ways of following up patients exposed to contaminated Viracept, other measures will also be introduced, such as closer monitoring of side effects reported in patients who have taken Viracept.
What measures are being taken to prevent similar problems occurring in the future?
The manufacturing site in Switzerland where the contamination happened has been inspected. The report from the inspectors highlights areas of concern and the company has prepared an action plan to address the reasons why the contamination occurred, and to prevent it from happening again.
The CHMP has recommended a set of corrective measures that must be put in place by Roche.
Will the action in Europe have an impact on other countries outside the EU?
The suspension of the marketing authorisation for Viracept will have an impact on the supply of this medicine to other countries outside the EU who rely on Viracept’s EU authorisation to allow it onto their markets. In case of concern, patients and healthcare providers outside the EU are advised to refer to the World Health Organization website. Canadian, Japanese and United States markets are not affected as they use a different source of nelfinavir mesilate.
The EMEA will update this document as new information becomes available.
©EMEA 2007 2/2
Posted: June 2007