Good Manufacturing Practices (GMP) deficiencies at Ben Venue Laboratories Inc, USA

This is an update regarding the recently identified deficiencies in the area of Good Manufacturing Practices (GMP) at the manufacturing site of the contract manufacturer, Ben Venue Laboratories Inc. (BVL) located in Bedford, Ohio, United States. A recent assessment by various regulators, including the US Food and Drug Administration (FDA) and Health Canada (HC) of the BVL manufacturing site had identified deficiencies in BVL's GMP, which may have an impact on the quality of the products manufactured there.

Background

BVL is a contract manufacturer of various injectable and inhalational medicinal products. Recently, a joint GMP inspection of the BVL site by regulators from the United Kingdom, France and the US had identified several shortcomings in their quality-management systems, particularly in relation to the aseptic filling process in the North complex of the Ben Venue facility. The deficiencies in the quality assurance could potentially have an impact on the quality of products manufactured at the BVL manufacturing site. In late November 2011, Ben Venue announced the voluntary shutdown of its manufacturing and distribution facilities and that it will investigate the GMP issues identified by the regulators. The supply of all BVL manufactured products have ceased since the shutdown of the BVL manufacturing and distribution facilities.

Local Situation and Advisory

Healthcare professionals have been updated by HSA on the GMP deficiencies of BVL and the potential impact it may have on the quality of the affected BVL manufactured products. Additionally, actions taken to address the products manufactured at the BVL manufacturing site are as follows:

a) BVL manufactured products that have an alternative manufacturing site

HSA has suspended the supply of all registered medicinal products manufactured by BVL that have alternative manufacturing sources eg, Velcade 3.5mg Injection® (bortezomib), Busulfex Injection® (busulfan), diluent for Torisel® Concentrate (temsirolimus). To ensure that the ongoing supply of these affected medicinal products continues to meet the needs of local patients, HSA had worked with the affected product licence holders to initiate the supply of the affected products from alternative manufacturing sources. All existing BVL manufactured stocks of these medicinal products were also replaced with supplies sourced from the alternative manufacturing site.

b) BVL manufactured products that do not have an alternative manufacturing site

For BVL manufactured medicinal products that do not have an alternative manufacturing source but had been identified to be critical for patients' needs, eg, Caelyx® (liposomal doxorubicin), existing stocks should only be used to complete treatment that has been initiated and no new patients should be initiated on Caelyx® treatment until further notice. Physicians were advised to consider other treatment alternatives.

HSA is monitoring the situation and will ensure that the affected products meet our regulatory requirements before being allowed back into the local market. Healthcare professionals are advised to report adverse reactions such as infections suspected to be associated with the use of products manufactured by BVL to the Vigilance Branch and to include the relevant clinical details of the adverse reactions and batch numbers of the affected product.