Federal inspectors say the contract manufacturer for Johnson & Johnson's cancer drug Doxil hasn't been maintaining equipment or promptly investigating defective product batches and other serious problems at its Bedford, Ohio, factory.
The latest Food and Drug Administration inspection report details lax quality control, failure to follow standard procedures and even lack of follow-up about a container of urine found in the Ben Venue Laboratories Inc. facility, which makes sterile medicines.
Doxil is one of a record 251 medications reported unavailable or in short supply in the U.S. this year, most of them injected drugs crucial for hospital operations. The crisis, blamed on at least 15 deaths, is disrupting patient care and clinical testing of new drugs being compared to or combined with older drugs in short supply.
Ben Venue is the sole supplier for Doxil, which has been in short supply since early summer and is no longer available for new patients.
First approved in 1995, Doxil is used to treat ovarian cancer, the bone cancer multiple myeloma and an HIV-related cancer called Kaposi's sarcoma. Currently, only 2,000 U.S. patients are getting it, and another 2,240 are on a waiting list, according to New Brunswick, N.J.-based J&J.
Ben Venue, part of German drugmaker Boehringer Ingelheim, said three weeks ago that it was temporarily halting manufacture and distribution of all products made at the Bedford plant. It cited an internal review indicating that routine preventive maintenance and tests to ensure manufacturing equipment is operating properly "did not occur at the specified time interval and is overdue."
Ben Venue spokesman Jason Kurtz said Thursday in an e-mailed response to The AP that the company is "working diligently to assess and implement the appropriate corrective actions to address the observations of the FDA investigators."
"Our highest priority is the delivery of safe and effective products to patients," he wrote. "We are continuing to work closely with the FDA with the goal of bringing the products we make back to patients as quickly as possible."
The inspection report posted this week on the FDA's website, covering visits to the factory from Nov. 7 through Dec. 2, details numerous deficiencies not promptly resolved or reported to plant managers. Some problems labeled as "critical" by the factory's quality unit were downgraded to "major" without justification, and the plant's vice presidents for operations and quality were unaware of them when the FDA inspectors asked about them.
The report notes:
_An investigation was opened on Sept. 19 on a 10-gallon can, found in a storage area, that contained a liquid that testing later indicated was urine. Follow-up was "past-due" at the time of the FDA inspectors' visits. Kurtz wrote Thursday that the container of liquid "consistent with urine" was reported to local police and the investigation remains open.
__Monitoring of air samples in manufacturing areas identified microbial contaminants, but Ben Venue did not identify their sources.
_The company doesn't have data showing its "manufacturing process consistently produces product meeting an acceptable level of sterility assurance."
_As of four weeks ago, there were "approximately 107 required preventive maintenance activities" at least 30 days past their scheduled due date.
_Quality-control staff lacked the training, technical expertise and oversight to perform their duties.
Johnson & Johnson spokeswoman Lisa Vaga said J&J does not know when Ben Venue will again be able to ship Doxil, but it has been working on finding additional suppliers since the summer and has found an alternate. The transition will require "an extended period," she said.
Ben Venue announced on Aug. 18 that it would be transitioning out of contract manufacturing over the next several years. That decision followed a May report by FDA inspectors at the same factory stating that, despite complaints dating back to August 2006, the company still had not identified the cause of metal particles contaminating two products that had been distributed. The names of the products were blacked out in the report.
Johnson & Johnson warned doctors on June 21 that it anticipated a shortage of Doxil, which has no generic alternatives. In August, it started a rationing system to allocate Doxil as supplies became available to patients who had started treatment.
As the drug shortages have mounted, President Obama on Oct. 31 ordered the FDA to take several steps to resolve and prevent shortages. The FDA and several members of Congress have been holding hearings since September to identify reasons for and possible solutions to the shortages.
The causes include manufacturing deficiencies leading to production shutdowns, companies ending production of some drugs with tiny profit margins, consolidation in the generic drug industry and limited supplies of some ingredients.