Inspections, Compliance, Enforcement, and Criminal Investigations
Gyrus Medical 1/10/11
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
10903 New Hampshire Avenue
JAN 10 2011
VIA United Parcel Service
Mr. Simon Edwards
Executive Managing Director
Gyrus Medical Limited
Fortran Road, St. Melons
Cardiff CF3 0LT
Dear Mr. Edwards:
During an inspection of your firm located in Cardiff, United Kingdom, on August 2-5, 2010, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures products intended for endoscopic and electrosurgical applications. Under section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. 321(h), these products are devices because they are intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or are intended to affect the structure or function of the body.
This inspection revealed that these devices are misbranded under section 502(t)(2) of the Act 21 U.S.C. 352(t)(2), in that your firm failed or refused to furnish material or information respecting the device that is required by or under section 519 of the Act, 21 U.S.C. 360i, and Title 21 Code of Federal Regulations (CFR) Part 803 - Medical Device Reporting (MDR) regulation.
We received responses from you, dated August 20, 2010 and October 6, 2010, concerning our investigator’s observations noted on the Form FDA 483, List of Inspectional Observations that was issued to you. We address these responses below, in relation to each of the noted violations. These violations include, but are not limited to, the following:
Failure to develop, maintain, and implement adequate MDR procedures, as required by 21 CFR Part 803.17. For example:
1. Your MDR Procedure failed to include the address where Medical Device reports need to be sent.
We reviewed your response, dated August 20, 2010, which includes your revised MDR Procedure. Your revised MDR Procedure, QSP-8.9, includes the address where medical device reports need to be sent. Your response to this observation appears to be adequate.
Our review of your MDR procedures collected during the establishment inspection revealed additional violations of the MDR regulation that were not noted as observations on the Form FDA 483, as follows:
2. Your MDR Procedure limits the reportability of adverse events to “unanticipated serious deterioration in state of health, sealing, cross contamination, mislabeling and loss of function.” You should evaluate each complaint that you receive for reportability. Your firm is required to submit reports to FDA whenever you receive information that “reasonably suggests” that your device:
“may have caused or contributed to a death or serious injury; or has malfunctioned and the malfunction would be likely to cause or contribute to a reportable death or serious injury if the malfunction were to recur.”
3. Your definition of “Serious injury” and “malfunction” is not consistent with 21 CFR 803.3. A serious injury is defined in 21 CFR 803.3 as an injury or illness that (1) is life threatening, (2) results in permanent impairment of a body function or permanent damage to a body structure, or (3) necessitates medical or surgical intervention to preclude permanent impairment of a body function or permanent damage to a body structure. A device malfunction is reportable, if a device or a similar device marketed by the manufacturer would be likely to cause or contribute to a death or serious injury if the malfunction were to recur.
4. Your MDR procedure does not include a timeframe for submitting supplemental reports to FDA, as required by 21 CFR 803.56.
5. Your MDR procedure combines language from the requirements of other regulatory competent authorities (i.e. Europe, Canada, Japan and Taiwan) with those from 21 CFR 803, which may cause confusion leading to incomplete, inadequate or even non-reporting of adverse events that meet the reportability requirements.
Please notify this office in writing within fifteen (15) working days from the date you receive this letter of the specific steps you have taken to correct the noted violations pertaining to the MDR regulation deficiencies including an explanation of how you plan to prevent these violations, or similar violations, from occurring again. Include documentation of the corrective action you have taken. If your planned corrections will occur over time, please include a timetable for implementation of those corrections. If corrective action cannot be completed within 15 working days, state the reason for the delay and the time within which the corrections will be completed. Please provide a translation of documentation not in English to facilitate our review.
Your response should be sent to: Paul Tilton, 10903 New Hampshire Avenue, WO-66, Room 3540, Silver Spring, Maryland 20993. If you have any questions about the content of this letter please contact: Paul Tilton at 301-796-5770.
In addition, FDA noted nonconformances with the Current Good Manufacturing Practice (CGMP) requirements of the Quality System (QS) regulation found 21 CFR Part 820. These nonconformities include, but are not limited to, the following:
1. Failure to establish and maintain adequate procedures to ensure that equipment is routinely calibrated, inspected, checked, and maintained, as required by 21 CFR 820.72(a). For example, there is no documentation to show the (b)(4) and (b)(4) test timers were calibrated. The Manufacturing Engineering Manager stated the timer does not need to be calibrated because the firm checks the timer with a (b)(4). However, there was no record of a (b)(4) being used to check the timers.
Your responses, dated August 20, 2010 and October 6, 2010, appear adequate. They state that a new calibration instruction has been created for (b)(4). Re-calibration of units (b)(4) and (b)(4) has been performed verifying the results are conforming. Additionally the preventative maintenance file has been updated for (b)(4), to include specific calibration requirements. A systemic corrective and preventive action is to be undertaken of all equipment which is currently specified as maintenance only to determine if any calibration requirements exist and to ensure any calibration requirements identified are defined and conducted appropriately. The expected completion dates are October 22 and November 19, 2010 and can be reviewed during the next inspection.
2. Failure to establish and maintain adequate procedures for monitoring and control of process parameters for validated processes to ensure that the specified requirements continue to be met, as required by 21 CFR 820.75(b). Specifically, the Director of RA/QA stated that dose audits are conducted per ISO 11137 standard – Sterilization of health care products – Radiation. However neither the Electrode Sterilisation Data document 940417 nor the (b)(4) Dose Audit Product Bioburden Monitoring document 920490 contained a specification that identifies the dose used during quarterly dose audits is to be established per the requirements of ISO 11137.
Your responses, dated August 20, 2010 and October 6, 2010, cannot be determined at this time. Amendments have been made to improve the clarity of document 940417 which specifically quotes the verification dose range in accordance with ISO 11137. Procedure 920490 has been modified to specify the requirements for compilation and evaluation of the report data. However, it cannot be determined if any additional documents may need to be updated with this information, as well.
3. Failure to establish and maintain adequate procedures to ensure that Device History Records (DHR’s) for each batch, lot, or unit are maintained to demonstrate that the device is manufactured in accordance with the Device Master Record (DMR), as required by 21 CFR 820.184. For example, the device history record for the Epoch electrode device does not document the completion of all steps required by the Epoch control plan. The Epoch control plan calls for operations to be performed on the Epoch electrode device, such as electrode preparation and leveling of the electrode device. The device history records do not include documentation of the electrode preparation and leveling of the electrode steps.
Your responses, dated August 20, 2010 and October 6, 2010, appear adequate. The responses included a review and update of the Epoch Risk Assessment 888185 and Control Plan 920804 to ensure completeness and correlation of relevant documents. The response also included a review and required update of all Manufacturing Plans, Control Plans manufacturing documentation and device History Record documentation to ensure the completeness and correspondence of these documents that are in progress. A global systemic CAPA has been completed to update the existing Manufacturing and Control Plan Procedure, document 920548 and train manufacturing and quality engineering staff in the revised Manufacturing and Control Plan Procedure.
4. Failure to establish and maintain a quality plan which defines the quality practices, resources, and activities relevant to the devices that are designed and manufactured, as required by 21 CFR 820.20(d). For example, the Director of RA/QA stated that your firm had no document that was specifically titled a quality plan.
Your response to this observation appears to be adequate. You provided an example of a Quality plan, document number 897040 illustrating the typical actions taken on each design product. Although your firm had a quality plan during the inspection, you failed to provide it to the investigator upon request. Your firm has also incorporated a policy defining Quality Planning into your Quality System which was completed and submitted in your updated response dated October 6, 2010.
Finally, you should know that this letter is not intended to be an all-inclusive list of the violations at your facility. It is your responsibility to ensure compliance with applicable laws and regulations administered by FDA. The specific violations noted in this letter and in the Inspectional Observations, Form FDA 483 (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 should investigate and determine the causes of the violations, and take prompt actions to correct the violations and to bring your products into compliance.
Steven D. Silverman
Office of Compliance
Center for Devices and