Regulatory Focus™ > News Articles > FDA Puts Japanese Manufacturer on Import Alert after Disastrous Inspection

FDA Puts Japanese Manufacturer on Import Alert after Disastrous Inspection

Posted 02 April 2013 | By Alexander Gaffney, RAC

A Japanese manufacturer of active pharmaceutical ingredients is now subject to an import alert after the US Food and Drug Administration (FDA) found it used significantly deficient practices in the manufacture of its products, including using machines that were rusty, corroded and contaminated.

Warning Letter: Rust, Bugs and Commingled Powders

The deficiencies were outlined in a Warning Letter sent by FDA to Asada Milling Co of Gunma, Japan sent on 22 March 2013 and made public on 2 April 2013.

FDA's warning letter references a number of alleged deficiencies, including several notable for their severity.

In one instance illustrated by FDA, the company was observed to have used manufacturing equipment that was corroded, rusted, had chipped paint and was "coated with an unidentified white powder."

"In addition, visible powder was observed on the equipment, floors, and walls of the mixing, [redacted] rooms of the facility," continued FDA, which explained that it was particularly concerned that the powders were from either-or both-types of APIs manufactured at the facility, which could lead to cross-contamination and adulteration of the products.

Asada had other, more general sanitary deficiencies as well, FDA said. For example, FDA said it was unable to find written procedures or established schedules for facility sanitation and manufacturing equipment maintenance, which likely led to the previously mentioned deficiencies.

But that lack of sanitation resulted in something a bit more disturbing: Hundreds of insects stuck in insect catchers, some of which were located in "close proximity" to manufacturing equipment. Those findings were made even after the company was made aware of their presence just two weeks prior, which FDA pointed out in its own inspection report.

Testing and Identification Problems

Other alleged deficiencies outlined in FDA's warning letter speak to more fundamental failings, such as the company's alleged lack of raw materials testing. Those materials go into the production of APIs, and good manufacturing practices call for companies to make sure they know the identity of what goes into their products. At Asada, however, FDA said there were "no established procedures that describe the receipt, identification, quarantine, or storage of raw materials," and noted that the company had not established specifications for either the raw materials or its finished APIs.

FDA said those deficiencies extended to testing API stability characteristics, which the company was alleged not to have completed in at least one instance. Elsewhere, FDA said the company had no written procedure for assigning lot numbers to API products, potentially hindering the ability to recall products because some of those lot numbers might not be unique.

Until all deficiencies are corrected, FDA said it may withhold approval of any new drug applications or supplements using the company as an API manufacturer.

The deficiencies are already cause for the agency to refuse to allow any direct articles manufactured by Asada into the US. An import alert issued on 2 April 2013 indicates that the company's products are subject to an import alert (#66-40) for all human and animal drug products manufactured at the Gunma-Ken facility.


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