Inspectors visited the San Francisco, California plant 13 times in 2011, culminating in the US Food and Drug Administration (FDA) sending Genentech a 483 with four main observations. Disintegration of vial washer gaskets and particles found in Avastin (bevacizumab) were the source of one concern.
“We noted that the investigation failed to include instructions to compare particulates isolated from culled Avastin finished drug product vials with the disintegrated gasket material”, the FDA wrote in the 483.
Genentech also failed to adequately document actions taken to fix an oil leak discovered when a capper power outage stopped an Avastin fill. Other concerns focus on the design of the capping area.
“The current design of the capping area…appears to allow a gap between the end of the HEPA filter coverage and the semi-permanent plastic barriers”, the FDA wrote. Air could pass through the gap and over vials during the conveyance and capping process.
The FDA also raises concerns about the use of contract service providers. Genentech uses studies run by a contract laboratory to set parameters for its displaced stopper detector but, the FDA says, it “lacks adequate documented evidence to support the integrity” of the service provider’s work.
Another problem is contract manufacture of Avastin vial caps. “There is no data to provide evidence that the current procedures and practices in place, including the contract manufacturing, shipment, handling, and administration of the caps do not result product adulteration”, the FDA wrote.
Caps are delivered to Genentech in “folded” plastic bags inside cardboard boxes, the agency wrote. The FDA wants Genentech to have data or controls to ensure cap integrity, particularly bioburden, is acceptable when shipping in non-sealed plastic bags.