Validation procedures lacking at IDev Technologies.(Medical Devices)

April 9--CDER

An inspection of IDev Technologies' corporate and production sites revealed GMP violations Dec. 9-Jan. 21. The company manufactures the SUPERA Interwoven Self-Expanding Nitinol Biliary Stent Delivery Catheter.

The investigator cited IDev for failure to establish and maintain adequate procedures for validating the device design, including failure of the design validation to ensure that the device conformed to defined user needs and intended uses; included testing of production units under actual or simulated use conditions; included risk analysis, where appropriate; and was documented. FDA wrote that the Houston, TX, firm's two acute animal study reports did not explain how testing in animals validated the use of the SUPERA stent delivery catheter for treatment of biliary strictures in humans.

The agency found IDev's response inadequate because its revised validation protocol did not state whether production devices would be used during the design validation, nor whether the design validation would need to be repeated "if your firm identifies design validation discrepancies during the design validation and corrects them, or provides convincing justification for not resolving design validation discrepancies, prior to production release."

FDA said that while some design validation discrepancies may not affect the intended use, they might prevent the product from meeting the needs of the user and patient, FDA wrote. For example, the agency noted, certain product defects may cause prolonged medical procedures.

The firm released a device design to production in June 2007 even though several design validation discrepancies detected during the animal study remained unresolved, FDA charged. The design validation discrepancies included several occurrences of ratchet joint failures, loose strain relief and cracked distal handles. The company initiated CAPAs in July 2007, yet these problems were not corrected until 2008.

IDev's response was inadequate because the company deemed certain failures to be low risk, and therefore did not require correction before production. "We do not consider the failure of the devices to deploy the stent in a patient a 'low risk' because the failure may result in a prolonged procedure or medical complications," FDA wrote.

The company also failed to establish and maintain procedures to ensure that the design requirements for its devices were appropriate and addressed the intended use of the device, the agency continued.

IDev did not define a specification for some aspects of the original design validation protocol, the design validation report and the SUPERA product specification. In the firm's response, it still had not defined or clarified some specifications, and therefore the response was inadequate.

IDev's product experience reports (PER) did not always include a complete description of events and/or subsequent investigation results for complaints of device malfunctions associated with the device's use in the vascular system--an unapproved use.

The agency acknowledged that the firm revised the complaint handling procedure to ensure that all events reported in a complaint will be better documented and investigated and initiated a CAPA to require an independent review of the complaint file to verify completeness and accurate documentation of reported device events. "Other parts of your response, however, are incomplete," FDA noted, including the firm's evaluation of unused, returned devices.

The agency also wrote: "Your firm's investigation of user complaints of stent elongation is not considered complete until your firm implements and verifies the effectiveness of the actions proposed in CAPA 3105 in order to (a) reduce incidents of ratchet fractures or slippage; and (b) confirm the definite root cause of stent elongation."

IDev did not maintain records of all communications with its sales representatives or hospitals, nor document a complete description of the cause that led to the market withdrawal of the Generation 1.0 and 1.5 devices, or that led hospitals to request the Generation 2.0 devices as documented in three nonconforming product reports. A CAPA documented that the catheter's ratchet shaft experienced field failures and that the firm initiated three design actions in the next model (Generation 2.0 devices) to correct this field failure.

The company's response was inadequate because, FDA wrote, "You have not explained whether and how the new design of the Generation 2.0 devices will correct the underlying design discrepancies in the previous design of the Generation 1.0 and 1.5 devices discussed in CAPA 3094. There appears to be a potential connection between these devices' field failures and their subsequent returns from the field."

FDA cited IDev for failure to establish and maintain procedures for implementing corrective and preventive action. A CAPA concerning marker band dislodgement/removal during clinical procedures did not document the firm's investigation of why the existing crimping process needed to be more robust, or the validation results of the crimping process.

The company's response was inadequate, the agency judged. Although an IDev memorandum provided adequate detail about the investigation into the marker band dislodgement, the automated crimping process was still not fully validated to account for all process variability.

The two actions proposed for another CAPA concerning "ratchet slippage in catheter impeding stent deployment" had not been implemented at the time of the inspection, the FDA investigator found.

In deeming the response inadequate, FDA wrote: "We do not agree that a ratchet mechanism failure is not high risk because ratchet slippage or fractures, which could result in either impeding stent deployment or stent elongation, may prolong medical procedures or pose medical complications. Therefore, we consider ratchet failures, if not effectively mitigated, a nonconforming design requirement in that your device design may not meet the user's and patient's needs."

At the time of the inspection, the firm had not investigated and documented the cause of eight complaints of stent elongation, reported between July 9, 2007, and Dec. 11, 2008, FDA added.

IDev did not perform a process performance qualification of the marker band process using the manually actuated Marker Band Swager Machine, nor did it provide a justification for not doing so despite the fact that a CAPA documented occurrences of marker band dislodgement/removal during clinical procedures. "Your firm has not defined a bond strength specification of the marker band to the outer sheath of the stent catheters and a test method in order to verify that the marker band is secured to the outer sheath," FDA wrote.

The agency also said IDev's response was not adequate because the company "still has not fully validated the crimping process. Whether your firm uses a manual or an automated crimping process, it must fully validate that process, including performing equipment installation qualifications and process performance qualifications, in order to ensure that the product consistently meets its predetermined specifications."

Further, the firm still had not specified a bond strength for attaching the marker band to the outer sheath of the catheters, the agency noted. "You state that the marker band does not 'constitute a critical joint structural catheter joint.' We disagree, however, because medical intervention is required in order to remove the marker band and prevent serious injury if it becomes dislodged," the letter continued.

IDev failed to revalidate the ratchet forming process when it increased the sizes of the devices, the warning letter stated. Although a company engineering order stated that no validation was needed because the firm visually inspected the formed ratchets during production, FDA found the justification not adequate because it does not explain whether the visual inspection can detect microcracks and other defects in the distal end of the ratchet, and thus prevent occurrences of ratchet slippage in catheter impeding stent deployment in patients.

Also, the response did not explain if visual inspection could determine whether the number of products that failed to meet ratchet specifications declined significantly after IDev increased the sizes.

"Your response was vague as it did not state whether your firm performed a revalidation of the ratchet forming process when your firm relocated the ratchet forming machine from the contract manufacturer to your firm's production site," FDA wrote. CAPA; C-H; Design; QC/QS; Val

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