OIG: Government Inspections of Generic Drug Manufacturers Improve, but Work Remains

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By James Swann

May 5 — The Food and Drug Administration has made strides in inspecting generic drugmakers in the U.S. and overseas, but pending inspections remain, according to a report from the Department of Health and Human Services Office of Inspector General released May 5.

The report noted that the FDA took multiple enforcement actions against four generic manufacturers based in India (Sentiss Pharma, RPG Life Sciences Ltd., Hospira Healthcare India and Wockhardt Ltd.).

Overall, the FDA increased preapproval inspections of generic manufacturers by 60 percent between 2011 and 2013, according to the report, “FDA Has Made Progress on Oversight and Inspections of Manufacturers of Generic Drugs” (OEI-01-13-00600).

The OIG said Congress requested the inquiry after a high-profile case in which Indian drugmaker Ranbaxy pleaded guilty in 2013 to federal charges that it failed to follow manufacturing requirements and made false statements to regulators.

Ranbaxy paid $500 million to resolve civil and criminal cases over allegations of substandard generic drugs.

Surveillance Inspections

The OIG said that in addition to the uptick in preapproval inspections, the FDA began conducting surveillance inspections for the first time in fiscal year 2013.

Unlike preapproval inspections, which are undertaken before the FDA approves an Abbreviated New Drug Application (ANDA), surveillance inspections are focused on generic manufacturers identified as being high risk by a risk-based model.

Out of 589 surveillance inspections in FY 2013, the FDA ended up taking action against 20 manufacturers (seven domestic, 13 foreign), in the form of warning letters, import alerts, regulatory meetings and a letter.

The FDA-issued warning letters were all focused on major violations of current good manufacturing practices (cGMPs), while the import alerts allowed the identified generic drugs to be blocked from importation.

As an example, multiple warning letters to Wockhardt said the company impeded FDA inspections by denying record requests and preventing inspectors from observing the manufacturing process.

“FDA also noted problems with laboratory records and stated that it was ‘particularly concerned about Wockhardt’s ability to implement a robust and sustainable quality system,' as well as the lack of adequate washing and toileting facilities for workers; FDA had observed urinals without drainage piping and stagnant urine on the facility floor,” the OIG said.

Outstanding Preapproval Inspections

While overall preapproval inspections did increase, the OIG said that the FDA hadn't conducted all inspections requested by the agency's Center for Drug Evaluation and Research as of Dec. 31, 2013.

The report said that 24 percent of preapproval inspections requested in 2011 had yet to be conducted as of Dec. 31, 2013, and all of them were for foreign generic manufacturers.

The pending inspection requests were due to a lack resources, according to the FDA, and the agency said it expects “the percentage of inspections conducted to improve with additional funding from user fees from manufacturers of generic drugs,” the report said.

Inspection Parity

Additional findings in the report said that the FDA achieved inspection parity between foreign and domestic generic manufacturers in FY 2013. Out of the 589 surveillance inspections, 57 percent involved foreign manufacturers.

The FDA defines parity as an equal percentage of inspections between domestic and foreign manufacturers, plus or minus 20 percent.

However, the OIG said the FDA was unable to report on whether foreign and domestic inspections were performed at the same level of detail.

The report also found that while the FDA has encouraged generic manufacturers to register, the registry may not be accurate.

For example, out of 432 generic manufacturers listed as having approved ANDAs in 2013, 45 (10 percent) didn't match any entries in the FDA's registry.

The Generic Drug User Fee Amendments of 2012 (GDUFA) requires generic manufacturers to submit identification data to the FDA on an annual basis.

OIG Recommendations

The OIG recommended that the FDA:

• conduct all outstanding preapproval inspections;

• make sure all generic manufacturers are registering with the FDA, which could be accomplished by cross-checking the list of approved ANDAs with the registry, cross-checking the registry against other lists of generic manufacturers and issuing warning letters to generic manufacturers that fail to register; and

• make use of the authority to request records instead of, or ahead of, an inspection as a way to improve the FDA's inspection process.


The FDA agreed with all three recommendations, and said it's “committed to conducting both generic preapproval and routine inspections in a timely manner.”

As for using the authority to request records instead of conducting an inspection, the FDA said it's working on developing “policies, guidance and pilot projects to implement this authority.”

To contact the reporter on this story: James Swann in Washington at jswann1@bna.com

To contact the editor responsible for this story: Kendra Casey Plank at kcasey@bna.com


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