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The European Medicines Agency is currently reviewing shortcomings in quality assurance identified during an inspection at Ben Venue Laboratories, Ohio, USA, where a number of centrally and non-centrally authorised medicines are manufactured. The Agency’s Committee for Medicinal Products for Human Use (CHMP) is assessing the impact on the quality of centrally authorised medicines manufactured at the site1. While the assessment is ongoing, the CHMP has recommended, as a precaution, the recall of all batches of Busilvex, Ecalta2, Luminity, Velcade, Vidaza and Vistide manufactured at Ben Venue, and specific measures for Caelyx, Ceplene and Torisel2 which are not being recalled.
1 The CHMP assessment is being conducted in the context of a formal review under Article 20 of Regulation (EC) No 726/2004, initiated at the request of the European Commission on 17 November 2011.
2 Made of two components: a powder or concentrate and a diluent. Only the diluent is manufactured at Ben Venue.- Which medicines are affected by the Agency’s review?
The Agency’s review covers the following centrally authorised medicines manufactured at Ben Venue Laboratories: Angiox, Busilvex, Caelyx, Cayston, Ceplene, Ecalta, Luminity, Mepact, Soliris, Torisel, Velcade, Vibativ, Vidaza and Vistide. They are sterile medicines delivered by injection, used to treat certain types of cancer, infections, a rare genetic disease and to detect and treat certain heart problems3 .
A number of non-centrally authorised medicines are also manufactured at this site and are being assessed by EU Member States taking a similar approach to the Agency’s review. If they are marketed in several EU countries, this is being coordinated by the Co-ordination Group for Mutual Recognition and Decentralised Procedures for human medicines (CMDh).
3 More information on these medicines can be found in the relevant European public assessment reports (EPARs) for each medicine.
- Why are these medicines being reviewed?
A Good Manufacturing Practice (GMP) inspection of Ben Venue in November 2011 highlighted several shortcomings in the quality-management system in place at Ben Venue, particularly in relation to the sterile filling process and possible particle contamination during the manufacturing process4. During the inspection, Ben Venue decided to cease all manufacture and distribution of medicines from its site.
The causes and impact of the possible particle contamination and the sterility assurance problem are currently being assessed.4 The November 2011 inspection of the Ben Venue Laboratories manufacturing site was conducted by the Medicines and Healthcare Products Regulatory Agency (MHRA) and the Agence Française de Sécurité Sanitaire des Produits de Santé (AFSSAPS) jointly with the Food and Drug Administration (FDA) as a follow-up to a previous inspection conducted in March 2011 that had been triggered by the European Medicines Agency as part of a re-inspection program. This inspection had already led to the restriction in the importation of some medicines to the EU from the Ben Venue site.
- How is the CHMP assessing the impact on centrally authorised medicines produced at this site?
The CHMP is conducting an assessment on the benefits and risks for each medicine concerned. For each product the CHMP has considered whether supply from Ben Venue is essential to meet patients’ clinical needs, taking into account the availability of alternative treatments, the quantity of the medicine currently in stock in the EU, and the possibility of sourcing the product from alternative manufacturers.
- What are the interim recommendations of the CHMP?
Given the potential risks identified, as a precautionary measure, the CHMP is recommending that only products that are absolutely essential for patients and for which no alternative supplier is available should continue to be used. On the basis of the currently available information, the CHMP is making the following interim recommendations in order to protect public health while the inspection and review are being finalised:
Caelyx, Ceplene and Torisel
The CHMP considers supplies of Caelyx, Ceplene and Torisel from Ben Venue to be essential for patients and that existing stocks in the EU should remain available to them, as Ben Venue is the only manufacturing site for these medicines. The Committee is issuing the following recommendations for these products:
- For Ceplene and Torisel, healthcare professionals are advised to visually inspect any vials for particles prior to administration. For Torisel, only the diluent and not the concentrate for infusion is manufactured at Ben Venue. Therefore the diluent vial should be inspected. No supply shortage is foreseen, but the marketing authorisation holders must identify alternative manufacturing sites to guarantee future supply.
- For Caelyx, there is an ongoing supply shortage, and the CHMP has issued detailed recommendations which have been sent in writing to healthcare professionals. Patients already receiving Caelyx may continue their treatment for as long as supplies last but no new patients should be started on Caelyx.
Busilvex, Ecalta, Luminity, Velcade, Vidaza and Vistide
The CHMP recommends, as a precaution, that all batches of Busilvex, Ecalta, Luminity, Velcade, Vidaza and Vistide manufactured at Ben Venue be recalled from the EU market. Recalling batches of these medicines supplied by Ben Venue will not impact on patients since alternative manufacturers are supplying the EU market with these products. Luminity, which is for diagnostic use, has been produced but not yet distributed in the EU (stock is currently quarantined by the marketing authorisation holder).
Angiox and Mepact
The CHMP is not currently recommending any urgent measures. Mepact is unlikely to be affected because it is filtered before use and Angiox is manufactured at a site for which no problems have been identified to date.
Cayston, Soliris and Vibativ
The CHMP is not recommending any urgent measures for these medicines while the review is ongoing because supplies from Ben Venue are not currently available on the EU market.
- What are the recommendations for healthcare professionals?
- Angiox, Ceplene, Mepact and Torisel can continue to be used. For Ceplene and Torisel however, healthcare professionals are advised to visually inspect the vials for Ceplene and Torisel diluent for particles before giving them to patients.
- No new patients should be started on Caelyx. Existing Caelyx stocks, while they last, should only be used to complete treatment that has already been initiated. In addition, healthcare professionals should monitor treated patients intensively and report immediately any relevant safety concerns (including sepsis or suspected sepsis) that could be evidence of a quality assurance problem with the sterilisation process.
- Pharmacists have been notified of the recall of Busilvex, Ecalta, Luminity, Velcade, Vistide and Vidaza in writing. Affected batches should be identified and returned to the supplier.
- What are the recommendations for patients?
- Patients should report any adverse reactions to their doctor or pharmacist.
- Patients who have any questions or concerns about their treatment should speak to their doctor or pharmacist.
- What will happen next?
These are interim measures issued in order to protect public health while the inspection and the review are being finalised. The European Medicines Agency will provide updates as soon as new information becomes available.
| Name | Language | First published | Last updated |
|---|---|---|---|
| Questions and answers on shortcomings in quality assurance at Ben Venue Laboratories | (English only) | 13/12/2011 |
Press release
European Medicines Agency recommends precautionary recall of remaining batch of Vistide manufactured at Ben Venue Laboratories
The European Medicines Agency has recommended a precautionary recall at pharmacy level of one batch of the antiviral medicine Vistide, which is used to treat cytomegalovirus infections of the retina. This is part of the continuing review of the shortcomings in quality assurance identified during a good manufacturing practice (GMP) inspection at Ben Venue Laboratories’ manufacturing site in Ohio, USA, and their impact on centrally authorised medicines manufactured at this site.
During its initial review in November 2011, the Committee for Medicinal Products for Human Use (CHMP) considered that supplies of Vistide manufactured by Ben Venue could continue to be used, as this medicine is sterilised at the end of the manufacturing process and thus there is no risk of lack of sterility. However, the GMP inspection has now revealed a possible contamination with particles and the CHMP concluded that the sterilisation at the end of the manufacturing process could not guarantee the absence of particles in the vial. Recalling one batch of this medicine supplied by Ben Venue will not lead to a product shortage since an alternative manufacturer of Vistide is now supplying the European Union market. Therefore, the CHMP now recommends the recall of the remaining batch of Vistide manufactured at Ben Venue as a precautionary measure.
The inspection process and the review of all centrally authorised medicines manufactured at the Ben Venue Laboratories plant is still ongoing and the Agency will make further updates as appropriate.
Note
- The European review of the centrally authorised medicines Angiox, Busilvex, Caelyx, Cayston, Ceplene, Ecalta, Luminity, Mepact, Soliris, Torisel, Velcade, Vibativ, Vidaza and Vistide, manufactured at the Ben Venue site in Ohio, is being conducted in the context of a formal review, initiated at the request of the European Commission under Article 20 of Regulation (EC) No 726/2004, on 17 November 2011. More information on these medicines can be found in the relevant European public assessment reports (EPARs).
| Name | Language | First published | Last updated |
|---|---|---|---|
| European Medicines Agency recommends precautionary recall of remaining batch of Vistide manufactured at Ben Venue Laboratories | (English only) | 13/12/2011 |
Key Facts
- Related Medicine : Vistide
Name of related medicine Vistide Active substance cidofovir
Marketing authorisation holder Gilead Sciences International Ltd.
- Related Medicine : Vidaza
Name of related medicine Vidaza Active substance azacitidine
Marketing authorisation holder Celgene Europe Ltd.
- Related Medicine : Vibativ
Name of related medicine Vibativ Active substance telavancin
Marketing authorisation holder Astellas Pharma Europe B.V.
- Related Medicine : Velcade
Name of related medicine Velcade Active substance bortezomib
Marketing authorisation holder Janssen-Cilag International NV
- Related Medicine : Torisel
Name of related medicine Torisel Active substance temsirolimus
Marketing authorisation holder Pfizer Limited
- Related Medicine : Soliris
Name of related medicine Soliris Active substance eculizumab
Marketing authorisation holder Alexion Europe SAS
- Related Medicine : Mepact
Name of related medicine Mepact Active substance mifamurtide
Marketing authorisation holder IDM Pharma SAS
- Related Medicine : Luminity
Name of related medicine Luminity Active substance perflutren
Marketing authorisation holder Lantheus MI UK Ltd.
- Related Medicine : Ecalta
Name of related medicine Ecalta Active substance anidulafungin
Marketing authorisation holder Pfizer Limited
- Related Medicine : Ceplene
Name of related medicine Ceplene Active substance histamine dihydrochloride
Marketing authorisation holder Epicept GmbH
- Related Medicine : Cayston
Name of related medicine Cayston Active substance aztreonam lysine
Marketing authorisation holder Gilead Sciences International Limited
- Related Medicine : Caelyx
Name of related medicine Caelyx Active substance doxorubicin hydrochloride
Marketing authorisation holder Janssen-Cilag International N.V.
- Related Medicine : Busilvex
Name of related medicine Busilvex Active substance busulfan
Marketing authorisation holder Pierre Fabre Médicament
- Related Medicine : Angiox
Name of related medicine Angiox Active substance bivalirudin
Marketing authorisation holder The Medicines Company UK Ltd.
| First Published | 13/12/2011 |
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| Last Updated | |
| Action |
All documents
| Name | Language | First published | Last updated |
|---|---|---|---|
| European Medicines Agency recommends precautionary recall of remaining batch of Vistide manufactured at Ben Venue Laboratories | (English only) | 13/12/2011 | |
| Questions and answers on shortcomings in quality assurance at Ben Venue Laboratories | (English only) | 13/12/2011 |
Related information
- Mepact: EPAR
- Vibativ: EPAR
- Caelyx: EPAR
- Torisel: EPAR
- Ceplene: EPAR
- Velcade: EPAR
- Cayston: EPAR
- Ecalta: EPAR
- Busilvex: EPAR
- Luminity: EPAR
- Vistide: EPAR
- Vidaza: EPAR
- Soliris: EPAR
- Angiox: EPAR
- Soliris: Pending EC decision
- Cayston: Paediatric investigation plan
- Soliris: Paediatric investigation plan
- Angiox: Paediatric investigation plan
- Ecalta: Paediatric investigation plan
- Torisel: Paediatric investigation plan
- Cayston: Paediatric investigation plan
- Soliris: Paediatric investigation plan
- Velcade: Paediatric investigation plan
- Ceplene: Orphan designation
- Torisel: Orphan designation
- Torisel: Orphan designation
- Vidaza: Orphan designation
- Vidaza: Orphan designation
- Soliris: Orphan designation
- Soliris: Orphan designation
- Mepact: Orphan designation
- Busilvex: Orphan designation
- Cayston: Orphan designation
- Velcade: Withdrawn application
- European Medicines Agency recommends transfer of manufacturing sites for Caelyx and Ceplene
- European Medicines Agency gives final recommendations for 12 centrally authorised medicines manufactured at Ben Venue Laboratories