Warning Letter Analysis: Medical Device Companies Cited for Marketing Unapproved Products

The US Food and Drug Administration's (FDA) latest batch of Warning Letters, released 6 June, cites three companies who are alleged to have violated current good manufacturing regulations and, in two cases, federal law by marketing unapproved products.

Siemens Healthcare Diagnostics (Medical Device)

In a 29 May warning letter sent to in medical device manufacturer Siemens Healthcare, FDA alleges the company's ADVIA Centaur iPTH immunoassay products manufactured at its Tarrytown, NY facility are adulterated because of current good manufacturing practice (CGMP) deficiencies present in their manufacture.

The agency identified no fewer than six design review problems within Siemens' CGMP procedures.

The company allegedly did not establish or maintain adequate design procedures to ensure appropriate design requirements. Specifically, a design development project lacked documentation of a formal review in the early stages of development, and another change was not assessed to determine if it required a premarket regulatory submission and regulatory approval.

Siemens was also cited for failing to establish or maintain a Global Regulatory Pre-Registration Worksheet when implementing design projects, failing to verifying the design of its device and failing to investigate an investigation into alleged design nonconformity problems.

FDA also said Siemens' Centaur device was misbranded as a result of its failure to make a 510(k) premarket notification to FDA or, alternatively, a premarket approval (PMA) submission.  As of 6 June 2012, Siemens seemed to have removed the product from those available for sale on its website, possibly indicating its removal from the market entirely.

Siemens also had several issues communicating with FDA. In responding to FDA's Form 483, which is an inspection report indicating any found deficiencies, the company provided FDA with an unsigned document returned after FDA's 15-day limit for responses. Siemens also asked FDA to view all attachments to the letter on a secure website, which FDA said it had and has no intention to do.

FDA did not comment on Siemens response to the warning letter, which was finally received in full form after the 15-day response window.

Copan Italia (In Vitro Diagnotic)

Italian medical device manufacturer Copan Italia, a maker of analysis equipment, was found by FDA to be manufacturing adulterated medical devices after allegedly failing to adhere to CGMPs for its Universal Transport Media and WASP analysis equipment.

FDA identified seven primary deficiencies in its inspection notice, including failure to establish process validation, failure to elucidate quality and process requirements, failure to establish procedures needed for corrective and preventive action (CAPA), failure to review and evaluate complains from all forms of media, failure to establish document controls and failure to prevent equipment contamination.

While Copan Italia responded to FDA's 14 May warning letter and indicated its intent to retrain employees and correct noted deficiencies, FDA explained its response was itself deficient in that it did not specify or elaborate upon the steps to be taken to correct the deficiencies.

"Your firm failed to provide evidence of implementation of the revised procedures and documentation showing that employees have been trained," FDA wrote. "In addition, evidence of consideration of a systemic corrective action to address these violations was not provided."

Tango3 LLC (Medical Device)

Simpsonville, Kentucky-based Tango3, a manufacturer of ozone-purified water storage tanks, was found to be marketing an adulterated medical device after suffering an extensive litany of CGMP and other manufacturing deficiencies.

Tango3 was further identified by FDA as lacking approval for a PMA or 510(k) submitted by the company or an IDE for testing an investigational product. The company was also found to have modified the system since releasing it into interstate commerce, which would require additional notification to FDA.

FDA also identified 16 alleged categories of deficiencies in its letter to Tango3, ranging from failure to maintain device history records, failure to train manufacturing staff, failure to process complaints, failure to implement a design review system, and failure to validate the design of the device before manufacturing.