Posted 20 June 2012
By Alexander Gaffney
The US Food and Drug Administration (FDA) sent warning letters in May 2012 to Siemens Healthcare Diagnostics, Inc and Terumo Medical Products Hangzhou Company Ltd accusing the companies of manufacturing adulterated products in violation of federally mandated Quality System Regulations (QSRs). For one of the companies, the warning letter effectively bars its products from being imported into the US.
In its 10 May warning letter to Siemens Healthcare Diagnostics CEO Michael Reitermann, FDA's New England District Director Mutahar Shamsi alleges the company's Walpole, Massachusetts facility is not conforming to current good manufacturing practices (CGMPs). As a result of the alleged deficiencies at the facility, all in vitro diagnostic devices manufactured at the facility are, as far as FDA is concerned, adulterated.
The roots of Siemens' manufacturing problems go deep, explained FDA, and cover the facility and at least two products manufactured at the facility. FDA identified eight facility-related deficiencies:
- Failure to establish, maintain, and consistently meet device validation specifications
- Failure to verify device design and address device failures
- Failure to verify production processes
- Failure to implement or document corrective and preventive action (CAPA) procedures in multiple instances
- Failure to investigate medical device failures
- Failure to evaluate more than 1,250 complaints received regarding the firm's iPTH device
- Failure to provide adequate instructions for end users with distributed medical devices
- Failure to maintain an adequate device history record, including the quantity manufactured
Siemens was also cited for purportedly failing to submit more than 15 reports to FDA regarding potential adverse events occurring as the result of a device malfunctions. Such reports are due to FDA within 30 days of the company being made aware of the malfunction.
"The information in the complaint files … reasonably suggests that the device malfunctioned and that the device or a similar device marketed by your firm would be likely to cause or contribute to a death or serious injury if the malfunction were to recur," FDA wrote. Additional reports related to information known to the company about interference with a device were similarly not reported to FDA in a timely manner, the agency said.
FDA also expressed its opinion that Siemen's iPTH devices are misbranded as the result of repeated instances in which the company withheld safety and market removal information from FDA, and subsequently failed to justify its actions when FDA learned of the infractions.
Terumo's Hangzhou, China-based facility was also the subject of CGMP complaints related to the company's quality system regulation program.
In a 9 May warning letter, the Center for Devices and Radiological Health's Steve Silverman, Director of the Office of Compliance, alleged two medical devices manufactured by the company were adulterated as the result of CGMP deficiencies identified at the facility.
Those alleged deficiencies include:
- Failure to ensure the validation of manufacturing processes through the validation of testing procedures
- Failure to maintain conformity requirement procedures
- Failure to ensure all re-tested products meet specifications through the documentation of activities
- Failure to validate statistical techniques used to validate manufacturing processes
- Failure to ensure the suitability of equipment for its intended purpose
In its warning letter, FDA called the warnings against Terumo "serious" and said it would refuse admission to the "adulterated" devices and said it would detain any products known to be passing through US Customs.