Inspections, Compliance, Enforcement, and Criminal Investigations
Arrow International, Inc. 16-Jun-05
Department of Health and Human Services
Public Health Service
RETURN RECEIPT REQUESTED
June 16, 2005
Carl G. Anderson, Jr., Chairman and Chief Executive Officer
Arrow International, Inc.
2400 Bernville Road
Reading, PA 19605
Dear Mr. Anderson:
During an inspection of your establishment, located in Reading, Pennsylvania, from December 2, 2004 through December 22, 2004, our investigator determined that you manufacture neonatal catheters. Neonatal catheters are medical devices as defined by section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act).
The above-stated inspection revealed that these devices are adulterated under 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 conformance with the Current Good Manufacturing Practice (CGMP) requirements for medical devices which are set forth in the Quality System regulation, as specified in Title 21, Code of Federal Regulations (CFR), Part 820. Significant deviations observed include, but ate not limited to, the following:
1. Failure of management with executive responsibility to ensure that an effective quality system has been fully implemented at all levels of the organization, 21 CFR 820.20, in that adequate corporate oversight has not been maintained at your neonatal catheter manufacturing site, NeoCare Division, located in San Antonio, Texas. For example,
a) Your internal audit procedures, .which specify that quality management systems are to be monitored and evaluated by the Arrow corporate internal audit program for all Arrow manufacturing sites, were not implemented for your NeoCare Division manufacturing facility;
b) Your regulatory submissions and compliance procedures, which specify that various premarket notifications for Arrow medical devices are to be maintained by Arrow corporate management, were not implemented for your NeoCare Division manufacturing facility; and,
c) Your complaint handling procedures, which. define specific Arrow corporate management responsibilities, were not implemented for your NeoCare Division manufacturing facility.
2. Failure to fully implement corrective and preventive action (CAPA) procedures; 21 CFR 820.100(a)(1), in that comprehensive analysis of product complaints and Medical Device Reporting for your NeoCare Division manufacturing facility was not put into practice.
3. Failure to validate computer software for its intended use according to an established protocol 21 CFR 820.70(i), in that no protocol had been developed for validation of your Complaint Management System software.
4. Failure to investigate complaints involving the possible failure of a device to meet its specifications in a timely manner 21 CFR 820.198(a)(1), for example Complaint Reference numbers [redacted].
The above-stated inspection revealed that a significant change was made to the design of your NeoPICC 1.9 Fr. Catheter in which the barium content was increased from [redacted] and the inner and outer diameter was increased: These, changes could significantly affect the safety or effectiveness of the device. Your NeoPICC 1.9 Fr. Catheter is misbranded under section 502(o) of the Act [21 U.S.C. 353(o)] in that a notice or other information respecting the modification to the device was not provided to the FDA as required by section and 510(k) and 21 CFR 807.81(a)(3)(i).
The NeoPICC 1.9 Fr. Catheter device with the increased barium content and increased diameter is adulterated under section 501(f)(1)(B) of the Act [21 U.S.C. 351(f)(1)(B)] in that it is a class III device under section 513(f) and does not have an approved application for premarket approval in effect pursuant to section 515(a) or an approved application for an investigational device exemption under section 520(g).
Additionally, the above-stated inspection revealed that your 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 any material or information required by or under section 519 respecting the device and 21 CFR Part 803 (Medical Device Reporting (MDR) regulation). Significant deviations include, but are not limited to, the following: failure to submit an MDR within 30 days of receiving or otherwise becoming aware of information that reasonably suggest that a marketed device may have caused or contributed to a death or serious injury, as required by 21 CFR 803.50(a)(1). For example, your firm failed to submit complaints (numbers [redacted] as serious injury MDRs within 30 days of becoming aware of the events, which involved the catheters eroding through the patient's vein wall.
This letter is not intended to be an all-inclusive list of deficiencies at your facility. It is your responsibility to ensure adherence to each requirement of the Act and regulations. The specific violations noted in this letter and in the FDA 483 issued at the close of the inspection may be symptomatic of serious underlying 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 must promptly initiate permanent corrective and preventive action for your quality system.
Federal agencies are advised of the issuance of all Warning Letters about devices so that they may take this information into account when awarding contracts. Additionally, no applications for premarket approval of 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.
You should take prompt action to correct these 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.
The Food and Drug Administration received your January 10, 2005, response to the inspectional observations, Form FDA 483 and your February 24, 2005, supplemental response to the Form FDA 483. Ceasing production of all NeoCare products and contracting a consultant appears to be an adequate response in the interim, however, the root cause for the medical device reports for the NeoPICC 1.9 Fr. Catheter has not been identified and Arrow International has not set a timetable for identifying and then correcting the root cause.
You stated that all memos-to-file have been transferred from the San Antonio facility to the corporate Regulatory Affairs department. This appears to be an adequate response for the violation that management with executive responsibility did not ensure that an adequate and effective quality system be fully implemented and maintained at all levels of the organization. You stated that protocol [redacted] has been revised to include the NeoCare product line facility and you will ensure that the NeoCare line will be included the 2005 corporate annual review.
In addition, you stated that Arrow Headquarters will process all complaints and all NeoCare Medical Device Reports will be filed by the corporate facility. This appears to be an adequate response. Protocol [redacted] Medical Device Reporting) now includes the NeoCare product line and the severity codes [redacted] are updated. FDA will revaluate Arrow's complaint handling at a future inspection. The supplernental response dated February 14, 2005, notes that [redacted] is being revised.further and that a revised copy will be provided in another supplemental response when completed. Please provide the revised copy for our review.
The Arrow Regulatory Affairs department agrees to review all engineering change orders for the NeoCare line and determine if a new 510(k) submission is required. Please provide those changes and the devices to which they apply to our Office of Device Evaluation for review.
You stated that the complaint handling protocol [redacted] includes the NeoCare line. Future inspections will determine if the complaint handling by Arrow is incompliance with [redacted].
You stated that a CAPA project for the NeoPICC 1.9 Fr. Catheter was opened. You stated that members of the Product Performance Group reviewed the [redacted] protocol. In addition, you stated that your firm added a CAPA field as part of the complaint management database and developed a CAPA checklist. These responses appear to be adequate for the violation that procedures addressing documentation of corrective and preventive action activities were not being implemented. A follow-up inspection by the FDA will determine if Arrow International follows its CAPA policy.
You stated that your firm developed a database field for the NeoCare product line in the Quarterly MDR Analysis Report (changed to monthly). This response appears to be adequate. This will be reviewed during the next inspection.
Also, you stated that you firm created a validation protocol to ensure that computer management software functionality is validated. This response appears to be adequate for the violation that software used as part of the quality system was not validated for its intended use according to an established protocol. Since it Will take several weeks for Arrow to determine the status of the validations of each software-coritrolled system the FDA will review the validation protocol at a follow-up inspection.
Please notify this office in writing within fifteen (15) working days of receipt of this letter, of any additional steps you have taken to correct the noted violations, including an explanation of each step being taken to prevent the recurrence of similar violations. 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.
Your response should be sent to William J. Forman, Compliance Officer, Food and Drug Administration, 2nd & Chestnut Streets, Room 900, Philadelphia, Pennsylvania 19106.
Thomas D. Gardine
Philadelphia District Office
Food and Drug Administration