On July 13, the Food and Drug Administration (FDA) issued an extensive warning to Richard L. Ernst, President and CEO of Hitachi Medical Systems America, Inc. of Twinsburg, Ohio.
The warning followed an inspection of Hitachi’s medical device manufacturing facilities in Twinsburg by an FDA investigator on March 16-18 and 24 and April 8, 11 and 12, 2005 with respect to the magnetic resonance imaging (MRI) systems manufactured by Hitachi Medical, Tokyo, Japan which are medical devices as defined in section 201(h) of the Federal Food, Drug and Cosmetic Act (the Act).
The above inspection revealed that Hitachi’s devices are misbranded in that the company failed to furnish material or information required under the Act and the Medical Device Reporting (MDR) Regulation.
Specifically, Hitachi had received complaints relating to four separate events for which it failed to submit an MDR to the FDA within 30 days of receiving information that the devices may have caused or contributed to a death or serious injury.
• One complaint documents an event involving a patient being scanned in Hitachi’s AIUS MRl device. During the scan, the system flashed an “unrecoverable error” message and continued to scan after the error message. The patient complained of heat on the right side of the head. The technologist noticed that the head coil had come unlatched on the right side of the patient. On 7/2/04, your firm received a letter from the patient complaining of daily headaches since the MRI scan in the area where the burns occurred. This event suggested that the device failed to perform as intended and may have caused or contributed to a serious injury. An MDR should have been submitted to FDA for this event.
• Two other complaints involved a patient being scanned in one of Hitachi’s AIRIS MRI devices. Both patients sent letters to Hitachi complaining of permanent tinnitus since being scanned. One of those patients had never experienced tinnitus prior to the MRI scan and so advised Hitachi in a letter and faxed to the company on 10/18/2002. The other patient had seen several otolaryngologists as well as a neuro-otologist regarding the tinnitus which still remains and the company was also advised of this in a letter of 11/20/02. Since the MRI may have caused or contributed to the tinnitus, MDRs should have been submitted to FDA for these two events.
• In another case, a patient being scanned in one of Hitachi’s AIRIS MRI devices of the MRI being too loud and was given an additional set of earplugs. After the exam, the patient claimed to have suffered hearing loss due to the noise in the MRI. The patient saw an audiologist the next day who confirmed the patient had suffered some hearing loss and had tinnitus and fullness in the right ear. The audiologist indicated the vibrations in the machine contributed to the problem. Again, an MDR should have been submitted to FDA for this event.
Although Hitachi claimed to have filed the above complaints (as well as an additional complaint that was not reviewed by the FDA investigator) as MDR events, the FDA found the company’s MDR procedure to be inadequate because it does not address several of the factors included in the definition of caused or contributed as defined in the MDR Regulation.
The warning letter also found Hitachi’s Altaire MRI systems were misbranded within the meaning of the Act in that a report of correction or removal was not submitted to FDA as required by the Act.
The Correction and Removal Regulation requires manufacturers and importers to promptly report to FDA, within 10 working days, any correction or removal of a device to reduce a risk to health. The FDA found three corrections and removals that Hitachi did not report to the agency.
• On December 17, 2004, Hitachi created a work instruction to visit all sites that owned an Altaire MRI and to inspect and tighten all gradient coils due to safety concerns. Hitachi created this work instruction because it had received a complaint that an Altaire MRI caught fire due to arching between connections.
• On November 18, 2004, Hitachi released field service instructions for all service representatives to visit each site that had an Altaire MRI and to inspect each compressor. According to the instructions, if the compressor contained a Type A absorber, it needed to be replaced, because these absorbers contained bad welds and were from an unauthorized supplier. Hitachi created these field instructions, because on October 18, 2004, it had received a complaint that an absorber unit on the helium compressor had cracked at the seam, and that the pressure released resulted in “an explosive force that bent the compressor covers and popped the screw heads making them “projectile.”
• On April 20, 2004, Hitachi issued a Software Release Bulletin instructing the service representatives to install a software upgrade to all Altaire/AIRIS MRI systems. This upgrade fixed the problem of images from one patient’s study being co-mingled with another patient’s study. Hitachi became aware of the co-mingling problem when it received complaints from two different customers stating that images from one patient’s study were co-mingled with another patient’s study. Both complaints also stated that the images were captured under one patient file.
The FDA warning noted that regulations require manufacturers and importers to promptly report to FDA any correction or removal of a device if the correction or removal was initiated to reduce a risk to health. The FDA concluded that because Hitachi’s actions met the definition of a “correction” in the regulations and because they were initiated to reduce a risk to health, Hitachi’s failure to report them until the issue was raised by the FDA investigator violated the applicable regulation.
The FDA also found Hitachi’s devices are “adulterated” within the meaning of the Act, in that the methods used in, or the facilities or controls used for manufacturing, packing, storage, or installation are not in conformance with the Quality System Regulation (QSR), as specified in the Code of Federal Regulations (CFR). The deviations from the QSR cited by the FDA include, but were not limited to, the following:
• Failure to ensure that all complaints are evaluated to determine whether the complaint should be filed as a Medical Device Report (MDR). Specifically, 4 of the 25 complaints reviewed by the investigator had not been evaluated to determine if they were medical device reportable events. For example, one complaint stated that a patient was shocked and burned on the top of her head while being scanned in the AIRIS MRI system. The complaint was not evaluated to determine if it was a medical device reportable event.
• Failure to verify or validate corrective and preventive actions to ensure that the action is effective and does not adversely affect the finished device. For example, a complaint dated 7/7/04, states that service personnel were disabling the internal interlock switch because gantry covers on the Sceptre PET system were coming loose. Additionally, service personnel were using epoxy to fix broken shoulder bolts. There were no verifications or validations performed for these corrective actions, and change control procedures were not followed.
• Failure to adequately inspect, test, or verify as conforming to specified requirements acceptance activities for incoming components. Specifically, Hitachi performed testing on only the first 4 AIRIS elite MRI Rapid Heat Coils used on the AIRIS elite MRI system. No subsequent incoming testing has been performed by Hitachi on incoming coils and there is no documented rationale or statistical basis for only testing the first 4 coils.
The letter stated that it “is not intended to be an all-inclusive list of violations at your facility. It is your responsibility to ensure compliance with applicable laws and regulations. The specific violations noted in this letter and in the Inspectional Observations, Form FDA 483 issued at the closeout of the inspection may be symptomatic of serious problems in your firm’s manufacturing and quality assurance systems. You are responsible for investigating and determining the causes of the violations identified by the FDA. You also must promptly initiate permanent corrective and preventive action on your quality system.”
The warning also cautioned Hitachi that: “Federal agencies are advised of the issuance of all Warning Letters about devices so that they may take this information into account when considering the award of contracts. Additionally, no premarket applications for Class III devices to which the Quality System regulation deficiencies are reasonably related will be approved until the violations have been corrected. Also, no requests for Certificates to Foreign Governments will be granted until the violations related to the subject devices have been corrected.”
Hitachi was instructed to “continue to take prompt action to correct any and all deviations. Failure to promptly correct these deviations may result in regulatory action being initiated by the Food and Drug Administration without further notice. These actions include, but are not limited to, seizure, injunction, and/or civil money penalties.”
Hitachi was given 15 working days in which to notify the FDA of the corrective actions it has taken for the deficiencies which the company has not previously addressed and for which the FDA has found corrective actions to have been inadequate.
The FDA will evaluate the adequacy of Hitachi’s corrective measures and procedures during the next FDA inspection. If Hitachi is unable to complete corrective action within the timeframes specified by the company, Hitachi must state the reason for the delay and the timeframe within which the corrections will be completed.