The FDA recently drafted guidance on what constitutes interference with inspectors doing their jobs, possibly leading the agency to tag a plant with an import ban. They may have been looking at a Form 483 they wrote up for Wockhardt's Waluj, India, plant when they laid out the violations, because a new warning letter excoriating the drugmaker says Wockhardt was guilty of many of them.
In May, the FDA placed the plant on import alert without giving specific reasons. But according to the warning letter posted Tuesday to its website, during a March visit quality-assurance personnel tried to hide records of batch failures, started to destroy test samples and told inspectors they had been given access to all areas of manufacturing for the U.S. The inspectors later learned of a cartridge-filling area they were not shown. All of those diversions show up in the guidance as the kinds of antics likely to land a plant on the import-alert list and even lead to criminal action by the agency.
The guidance was released last week, days ahead of the posting of the letter. It points out that there are sometimes good reasons for a company to ask for an inspection delay but is clear about what the FDA finds unacceptable. It says inspectors need to be able to copy records and take samples and photographs that provide a record of conditions. If plant managers keep inspectors from doing any of these things or prevent them from seeing manufacturing processes, the FDA says it is within its rights to stop the plant's products from being allowed into the country.
The Wockhardt warning letter is sprinkled with such findings. It says an inspector found trashed records and was given different records when the inspector asked that they be retrieved. The inspector went looking for the other records and found them hidden in another area. "Because you directed FDA investigators away from the requested documents, and because the FDA investigator was impeded by having to locate and reassemble torn records that FDA had requested and had the authority to inspect, you delayed the inspection," the warning letter reads. Similar language follows many of the observations.
The warning letter also said that when an investigator asked a quality-control analyst to describe the contents of unlabeled vials, the person "immediately began dumping the contents of the vials into the drainage sink" and then said the contents couldn't be determined. Inspectors said they found "unofficial" records on 75 batches that had problems from black particles to fibers and glass particles in them. The unofficial records showed up to a 14% failure rate on some batches, but investigators found that the problems were not investigated and official records showed that the batches all met specifications. There were also concerns about records lost during a computer "crash," given that a QC employee had the ability to delete records when the person should not have had that kind of access to the system. There are also questions about stability of drugs given that "trial" samples were taken, but records of any failures were not recorded. The "Production Head" lied to investigators about the practice, only confessing it later when confronted with statements from other employees that it was common.
On top of record-keeping problems, investigators found a toilet near the gowning area for the sterile manufacturing area where urine leaked from urinals and stood in a puddle near a drain. Mold and mildew were also found in the area. It said the plant had been warned about sanitation issues in the past.
Managing Director Murtaza Khorakiwala told Bloomberg in an email that it had hired a U.S. consulting firm to help it resolve the problems.
Some of these findings have overtones of the kinds of problems that led India's Ranbaxy Laboratories to its consent decree and a $500 million settlement with the FDA earlier this year. In that case, the FDA began to uncover problems in 2006 when inspectors found incomplete testing records and an inadequate program to check drug stability at Ranbaxy's Paonta Sahib, India, facility. Over the next 7 years, details of manufacturing quality failings dating back to 2003 and untrue statements to the FDA were exposed.
The problems at Wockhardt are expected to take a big financial toll on that company. Wockhardt has said the U.S. import ban could cost it $100 million in lost sales. Since then, the U.K. has followed suit this month with a ban that applies to drugs shipped there and the EU and recalled 16 Wockhardt drugs from the market. Reuters reports that the warning letter has led to analyst downgrades for Wockhardt shares, which Wednesday were off nearly 26% for the week. The company has said it has already started making changes at the plant, but Reuters reported Citigroup saying it expects fixes to take two years even though it maintained a buy recommendation on its shares.
- here's the warning letter
- read the Reuters story
- get more from Bloomberg