Inspections, Compliance, Enforcement, and Criminal Investigations
Northwest Medical Physics Equipment, Inc. 21-Dec-07
Department of Health and Human Services
Public Health Service
December 21, 2007
VIA CERTIFIED MAIL
RETURN RECEIPT REQUESTED
In reply refer to Warning Letter SEA 08-06
Northwest Medical Physics Equipment, Inc.
Mr. Andrew D. Jones
Director of Project Line, Management IGRT Solutions
1910 120th Place SE, Suite 101
Everett, Washington 98208
Dear Mr. Jones:
During an inspection of your firm located in Everett, Washington, on June 20, 2007, through June, 26, 2007, investigators from the United States Food and Drug Administration (FDA) determined that your firm manufactures the ISOLOC software used in the ACCULOC Image Guided Radiation Therapy (IGRT) System for radiation treatment of cancer patients. Under section 201 (h) of the Federal Food, Drug, and Cosmetic Act the Act), 21 U.S.C. § 321(h), this product is a device because it is intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or is intended to affect the structure or function of the body.
This inspection revealed that this device is adulterated within the meaning of section 501(h) of the Act (21 U.S.C. § 351(h)), in that the methods used in, or the facilities or controls used for, the manufacture, packing, storage, or installation are not in conformity with the Current Good Manufacturing Practice (CGMP) requirements of the Quality System (QS) regulation found at Title 21, Code of Federal Regulations (C.F.R.), Part 820. We received responses dated July 16, 2007, July 27, 2007, and November 5, 2007 from Mr. James A. Leong, Regulatory Affairs & Quality Manager, of CIVCO Medical Solutions, Kalona, Iowa, concerning our investigators' observations noted on the Form FDA 483, List of Inspectional Observations, that were issued to you on June 26, 2007. We address these responses below. These violations include, but are not limited to, the following:
1. Failure to establish and maintain procedures for receiving, reviewing, and evaluating complaints to ensure that complaints are evaluated to determine whether the complaint represents a medical device reporting (MDR) event, as required by 21 CFR 820.198(a)(3). Specifically,
a. Documentation of the 03/20/06 3:47 complaint did not include an evaluation of MDR reportability while the manufacturer stated that there was a risk of patient mistreatment.
b. Some complaints did not contain a signed MDR Evaluation section in accordance with the Complaint Procedure (NMP-02, Rev. G, 10/08/2004): 04/17/06 12:00; 04/11/96 22:26; 04/07/06 12:00; and 03/30/06 10:03.
2. Failure to establish and maintain procedures for receiving, reviewing, and evaluating complaint: to ensure that such procedures include; in the investigation records, a determination of: 1) whether the device failed to meet specifications; 2) whether the device was being used for treatment or diagnosis; and 3) the relationship, if any, of the device to the reported incident or adverse event, as required by 21. CFR 820.198(d). Specifically, the Medical Device Reporting and Vigilance System (NMP-01, Rev. H, 12/19/2006) and the Complaint Procedure (NMP-02, Rev. G, 10/08/2004) do not require such information:
3. Failure to adequately establish and maintain procedures for the identification, documentation, validation or where appropriate verification, review, and approval of design changes before their implementation, as required by 21 CFR 820.30(i).
a. You made changes to versions of the ISOLOC software between November 30, 2004, and April 7, 2006. For example, you released software patches for these various changes to your customers on November 30, 2004; December 30, 2004; April 11, 2005; April 28, 2005; May 31, 2005; January 2, 2006; and April 7, 2006. You have no documentation of validation or justification of verification for the seven patches. You also have no documentation of two incidents where problems were found with the patches that had been released. The ISOLOC 6.5 patch identified as 03102006 and issued on March 24, 2006, was removed from online distribution due to an "error" found in the patch which caused an inaccurate couch printout. You did not validate the patch or document that you had verified the correction.
b. Your "Design Control Procedure" (NMP-06, Rev. D, 10/06/2004), "Design Validation Procedure" (NMP-12, Rev. B, 08/21/2003)," and "Incident Management Procedure" (NMP-20, Rev. A, 09/05/2003) do not address the documentation, validation, or where appropriate verification, review, and approval of design changes before the implementation of software patches.
4. Failure to establish and maintain procedures for implementing corrective and preventive action to verify or validate the corrective and preventive action to ensure that such action is effective and does not adversely effect the finished device, as required by 21 CFR 820.100(a)(4): Specifically, your Change Order #06-018A documenting a bug in the ISOLOC software version 6.5, which was addressed in the Corrective Action Request Form #06-004 and corrected in the ISOLOC software version 6.6, does not indicate the results of the validation or verification testing and any re-evaluation of the risk analysis to ensure the effectiveness of the corrective action.
5. Failure to establish and maintain procedures for implementing corrective and preventive action to analyze processes, work operations, concessions, quality audit reports, quality records, service records, complaints, returned product, and other sources of quality data to identify existing and potential cause of nonconforming product, or other quality problems, as required by 21 CFR 820.100(a)(1).
Specifically, you have not statistically analyzed your complaints, CAPAs, and software problem reports on a regular basis as required by your "CAPA Procedure" (NMP-03, Rev. F), which has been in effect since June 29, 2006.
Our inspection also revealed that this device is 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 21 C.F.R. Part 803 - Medical Device Reporting (MDR) regulation, and 21 C.F.R. Part 806 - Reports of Corrections and Removals regulation. Significant deviations include, but are not limited to, the following:
1. Failure to submit MDRs to the FDA within 30 days of receiving or otherwise becoming aware of information that reasonably suggested that one of your commercially distributed devices has malfunctioned and would be likely to cause or contribute to a death or serious injury if the malfunction were to recur, as required by 21 CFR 803.50(a)(2). Specifically, your Corrective and Preventive Action (CAPA) and Complaint, dated December 9, 2005, described that there was a negative sign omission error upon manual data reentry for a patient receiving radiation treatment. The radiation therapy to the patient was not at the correct anatomical site due to the error in the software. The software error caused the ISOLOC 4.2 program to freeze and then multiply, location values after the software was rebooted. You have received three other complaints dated March 20, 2006, July 5, 2006, and July 24, 2006, where misadministration of radiation was delivered to cancer patients due to problems with the software. The information contained in the four complaints dated December 9, 2005, March 20, 2006, July 5, 2006, and July 24, 2006, suggest that your software would be likely to cause or contribute to a serious injury to a patient. There is no assurance that the software will operate correctly or that the correct alignment will be used during radiation therapy on a patient.
2. Failure to develop, maintain, and implement written MDR procedures, as required by 21 CFR 803.17. Specifically, the "Medical Device Reporting and Vigilance System" SOPs (NMP-01, Rev. H, 12/19/2006) were found to be incomplete. For example:
a. There is no written procedure that specifically addresses malfunction reporting (section 2.0) to ensure the timely and effective identification, communication, and evaluation of events that may be subject to MDR requirements (21 CFR 803.17(a)(1)).
b. The procedures list the FDA time schedule for various reports required by 21 CFR 803; however, the list (section 4.5.3) does not establish a procedure to describe how to identify and report these events to ensure the timely and effective identification, communication, and evaluation of events that may be subject to MDR requirements (21 CFR 803.17(a)(1)).
We note that the requirement of "Annual Certification" is listed in the procedures (section 188.8.131.52). However, this report should be deleted from the procedures since this requirement has been removed from 21 CFR 803.
3. Failure to submit correction and removal reports to FDA to remedy a violation of the act caused by the device which may present a risk to health (21 CFR 806.10(a)(2)) and to do so within 10-working days of initiating such correction and removal (21 CFR 806.10(b)). Specifically, reports were not submitted to FDA within 10 days of initiating corrections or removals for the seven software patches with recall numbers of Z-1145-07, Z-1146-07, Z-1147-07, Z-1152-07, Z-1153-07, Z-1154-07, and Z-1155-07 to reduce the risk of misadministration of radiation therapy.
Your firm's July 16, 2007, response is inadequate because it did not provide information to determine the extent of the corrective actions the firm had taken, or the corrective actions it will take at its Kalona facility in Iowa, to correct the deficiencies found during the inspection at Northwest Medical Physics Equipment, Inc. in Everett, Washington. Your firm's July 27, 2007, response is also inadequate because it did not specifically address the corrective actions that will be taken for the observations. For example, your firm's July 27, 2007, response provided copies of the MDRs for the four complaints cited in Observation 1 of the FDA 483. However, your firm's response did not address how your firm will correct and implement your MDR procedures to ensure that all complaints are properly received and reviewed. Further, your firm's November 5, 2007, response is inadequate. Specifically, as to Observation 1, you did not provide any documentation to FDA to verify that you have identified and reported all complaints found during the inspection. In addition, you stated that current complaints were going to be identified and evaluated by personnel in the Kalona facility in Iowa, but did not specifically address the corrective actions that will be taken at the Kalona facility to correct the deficiencies found during the inspection at Northwest Medical Physics Equipment, Inc. in Everett, Washington. Similarly, your responses to Observations 3, 4, 5, 6, 7, and 8 are inadequate because you did not specifically address the corrective actions that will be taken at the Kalona facility to correct the deficiencies.
You should take prompt action to correct the violations addressed in this letter. Failure, to promptly correct these violations may result in regulatory action being initiated by the FDA without further notice. These actions include, but are not limited to, seizure, injunction, and/or civil money penalties. Also, 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, premarket approval applications for Class III devices to which the Quality System regulation deviations are reasonably related will not be approved until the violations have been corrected. Requests for Certificates to Foreign Governments will not be granted until the violations related to the subject devices have been corrected.
Please notify this office in writing within fifteen (15) working days of receipt of this letter of the specific steps you have taken to correct the noted violations, 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 overtime, 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 send your reply to the Food and Drug Administration, Attention: Lisa M. Elrand, Compliance Officer, 22201 23rd Drive SE, Bothell, Washington 98021-4421. If you have questions regarding any issue in this letter, please contact Lisa M. Elrand at telephone (425) 483-4913 or telefax (425) 483-4760.
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.
Charles M. Breen