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U.S. Department of Health and Human Services

Inspections, Compliance, Enforcement, and Criminal Investigations

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Cook Group Inc. 6/24/11


Department of Health and Human Services' logoDepartment of Health and Human Services

Public Health Service
Food and Drug Administration
 Atlanta District Office
60 Eighth Street, NE
Atlanta, GA 30309

June 24, 2011

VIA United Parcel Service

Kem Hawkins, President
Cook Group Inc.
750 Daniels Way
Bloomington, IN 47402


Dear Mr. Hawkins:

During an inspection of your firm located in Winston-Salem, NC on 4/4-19/11, investigators from the United States Food and Drug Administration (FDA) determined that your firm manufactures the Cholangioscopy Access Balloon/ Direct Peroral Cholangioscopy Balloon (DPOC) and various gastroenterological and endoscopic devices. 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 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, their 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 (21 CFR), Part 820. We received a response from Dr. William S. Gibbons, President of Cook Endoscopy, dated May 6, 2011, concerning our investigators' observations noted on the FORM FDA 483, lnspectional Observations (copy attached) that was issued to Ms. Paula A. Joyce, Vice President of Quality Assurance/Regulatory Affairs. We address this response below, in relation to each of the noted violations. We received a second response from Dr. Gibbons dated June 21, 2011.

This response is currently under review. These violations include, but are not limited to, the following:

1. Failure to establish and maintain procedures for implementing corrective and preventive actions as required by 21 CFR 820.100(a). Specifically, several corrective and preventive actions (CAPAs) were deemed ineffective and corrective actions were not implemented in a timely manner. For example:

A) CAPA #10-16 was opened on 11/23/10 for the Cholangioscopy Access Balloon, a ductal anchoring device (DPOC), after the firm received reports of at least two patient deaths and two serious injuries due to air embolism and two reports of intrahepatic duct perforation due to inability to deflate the balloon. At least three malfunctions were also reported by users indicating inability to deflate the balloon. Your firm began manufacturing the DPOC devices for US distribution on 8/5/10 and recalled them on 1/7/11. You had not determined if the DPOC devices are permanently removed from the market. You had not adequately investigated the reported device failures and corrections to the device and/or actions to prevent re-occurrences have not been documented or implemented. CAPA #10-16 remains open.

A total of five incidents were received by your firm in which the balloons in the devices failed to deflate. You identified two risks namely air embolism and perforation. Your investigation into four of these five incidents concluded that the reports could not be confirmed because the products were not returned to the firm. The one case in which the device was returned, the report could not be confirmed due to the condition of the device. Your firm's root cause analysis indicates that your firm's Quality System does not give clear guidance for those devices that undergo little or no modification to generate a new device. You indicate that those devices may pose additional risks which would require additional risk mitigation. Your health hazard analysis indicates that further investigation is necessary.

Your response to this observation is inadequate because no thorough investigation was done to determine the root cause for the device failures. While you acknowledge that appropriate design control consideration will be exercised before market re-introduction of the Cholangioscopy Access Balloon (DPOC), no commitment was made as to the current status of the device. We acknowledge that on 6/21/11, you notified the Agency that you are voluntarily withdrawing your 510(k) for this device (K101095) out of an abundance of caution. You indicated that the adverse events reported with the use of this device were not the result of any defects with the device, but rather with the air from the optical devices that are used with the balloon.

B) Two CAPAs have been initiated for late adverse event reporting (CAPA #10-14 and #08-02}. The initial pattern of late reporting was noted in 1/2008 in CAPA #08-02 which was closed on 7/29/08. Our inspection revealed several MDRs were reported outside the 30 day timeframe.

Your response to this observation indicates that monitoring of this CAPA's effectiveness will be made over a 6-month period. You did not discuss actions your firm will take if corrective and preventive measures are found ineffective in the interim. You fail to address CAPA timeliness.

C) Your firm did not consider preventive actions when documenting corrections for example: CAPA #09-10 was opened on 10/13/09 to address numerous complaints that injection needle extensions were puncturing the outer sheath. Corrections implemented included educating customers on the proper manipulation of injection needles. No preventive actions were implemented and complaints are being received from new customers. This CAPA remains open as of the date of the inspection. Your firm's assessment of the corrective actions indicated that it was effective for the customers who had the devices prior to the CAPA, however since no preventive measures were put in place, new customers are experiencing issues of punctured outer sheaths for injection needle extensions.

Your response indicates that you have also established a (b)(4) monitoring period. Please refer to the response for Observation 1B. Your response to FDA 483 observation # 1Cb is inadequate in that no effectiveness monitoring period was assigned for implementing the new tensile tester or a specification revision.

D) Corrective actions are not implemented in a timely manner. For example, eight (8) out of ten (10) open CAPAs currently have been extended beyond previously established due dates. CAPA #09-10 had 3 extensions and remains open. CAPA #10-05 had 3 extensions and remains open as well.

Your response to this observation appears adequate.

2. Design verification does not confirm that design output meets design input requirements, as required by 21 CFR 820.30(f). Specifically, the design input that "user must be able to remove biliary stones from the ductal system" for Project 24001, Cholangioscopy Access Balloon, was not verified. Comments associated with this input indicate the balloon is the same as previously marketed extraction balloons. The documentation indicated the ductal anchoring device is a modified biliary duct extraction balloon. This specific design input was not verified. Further review of the Verification & Validation Traceability Table found other inputs which were not adequately addressed.

Your response to this observation indicates that you will review all open design projects as well as employee training on the revised design control procedures. You indicated that a follow-up report will be submitted to the Agency by June 30, 2011. We will review the follow-up report in conjunction with the response to this letter.

3. Risk analysis is inadequate, as required by 21 CFR 820.30(g). Specifically, you did not adequately identify known and potential risks during the design and development of the Cholangioscopy Access Balloon (DPOC) device. Risk reduction activities relied heavily on performance history of extraction catheters. In addition to reports of air embolisms and perforation, your firm received customer complaints of balloon ruptures during use, difficulty maintaining inflation during use, difficulty maintaining balloon position in the duct and difficulty advancing the endoscope over the balloon catheter during use. Your firm did not update your risk analysis to include these newly identified patient hazards and identify ways to mitigate these risks.

Your response indicated that the design-element-based Design Failure Modes, Effects, and Criticality Analysis (dFMECA) and Hazardous Situation and Preliminary Analysis training will be provided by June 30, 2011. Also, you indicated that a one year window of complaint data for each product family will be provided no later than June 30, 2011. This response is deemed inadequate since documentation was not provided.

4. Failure to establish procedures for the control of storage areas and stock rooms, as required by 21 CFR 820.150(a). Specifically, you have not established procedures to prevent mix-up of previously sterilized (sterile) devices and devices awaiting sterilization (non-sterile). Our investigators observed both sterile and non-sterile devices being stored in the same general area without physical separation. Both sterile and non-sterile devices are shipped out and returned from the sterilizer through the same warehouse doors in the same type shipping bins (sterilization baskets). Our investigators also observed a "STERILE" tag on an empty sterilizing basket that was staged to be used to fill non-sterile products.

Your response to this observation appears adequate. You indicated that a follow-up report to the Agency will be provided by June 30, 2011 addressing the relocation of the Quality Control (QC) packaging area. We will review. the follow-up report in conjunction with the response to this letter.

5. Failure to adequately establish procedures for identifying training needs and ensure that all personnel are trained to adequately perform their assigned responsibilities, as required by 21 CFR 820.25(b). Specifically, employees are not adequately trained to conduct investigations into the underlying causes for non-conformances and/or determine corrective/preventive actions.

Your response indicates that you will provide a follow-up report on employee training on Root Cause Investigation for CAPA as well as include a new Root Cause Analysis procedure implementation. You indicated that the follow-up report will be provided to the Agency no later than June 30, 2011. We will review the upcoming follow-up report in conjunction with the response to this letter.

6. Failure to adequately establish procedures for receiving, reviewing and evaluating complaints by a formally designated unit, as required by 21 CFR 820. Specifically, complaints are not investigated and evaluated within the (b)(4) timeframe outlined in the established procedure, Complaint Handling, QSP 13.0 dated 1/10/11. Several complaint investigations are past due. For example, the following complaints were not investigated: Complaint# 27571, 27697, 29007, 27772, 28944, and 28246.

Your response is inadequate since timelines for complaint investigation, review and closure are not clearly defined and expected closure dates have not been determined.

7. Failure to adequately establish procedures for finished device acceptance, as required by 21 CFR 820.80(d). Specifically, assembly and packaging of kits are performed by Quality Control personnel. The same personnel also perform kit release. No independent inspection, process or Device History Record reviews are done prior to final device release.

Your response indicated that a follow-up report for independent Device History Record (DHR) review process of sets and kits will be provided by June 30, 2011. We will review the adequacy of the follow-up report in conjunction with your response to this letter.

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 Food and Drug Administration 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 with fifteen (15) working days from the date you receive 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 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.

Your response should be sent to Serene N. Ackall, Compliance Officer at the address noted in this letterhead. If you have any questions about the content of this letter please contact Ms. Ackall at 404-253-1296. 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 lnspectional Observations (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.  



John R. Gridley, Director
Atlanta District