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U.S. Department of Health and Human Services

Inspections, Compliance, Enforcement, and Criminal Investigations

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APC Medical Ltd. 08-Oct-02

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

Public Health Service
Food and Drug Administration

 

Center for Devices and
Radiological Health
2098 Gaither Road
Rockville, Maryland 20850


 

October 2, 2002

VIA FEDERAL EXPRESS

WARNING LETTER

Mr. Gerald L. R. Burne
General Manage r
APC Medical Ltd.
68 Tewin Road
Welwyn Garden City, AL71BD
United Kingdom

Dear Mr. Burne:

During an inspection of your firm located in Welwyn Garden City, United Kingdom, on June 24-27, 2002, our investigator determined that your firm manufactures Temporary Cardiac Pacer Extension Cables (Reusable), Pacer Analyzer Cables (Sterile, Disposable), and Temporary Cardiac Pacers that are imported into the United States. These products are devices as defined by Section 201(h) of the United States Federal Food, Drug, and Cosmetic Act (the Act).

This inspection revealed that these devices are adulterated within the meaning of Section 501(h) of the Act, 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 Quality System Regulation as specified in Title 21, Code of Federal Regulations (CFR), Part 820, as follows:

1. Failure to maintain an adequate organizational structure to ensure that devices are being designed and produced in accordance with the Quality System requirements, as required by 21 CFR 820.20(b). For example, the organizational structure does not provide the necessary independence in that the General Manager has operational duties and responsibilities in routine assembly and quality control in addition to key elements of the quality system.

2. Failure to report on the performance of the quality system to management with executive responsibility as required by 21 CFR 820.20(b)(3)(ii). For example, the General Manager is both the management representative and management with executive responsibility. No evaluation has been made to determine if an alternative approach should be implemented to provide the independence necessary to ensure that quality system requirements are established and maintained.

3. Failure to establish and maintain plans that describe or reference the design and development activities and define responsibility for implementation, as required by 21 CFR 820.30(b). For example, a Design and Development Plan was not established for the Model 4265, 4265A, and 4265V Patient Extension Cables for use with external pacemakers. [redacted]

4. Failure to establish and maintain a Design History File for each type of device, as required by 21 CFR 820.30(j). For example, there is no Design History File for the Model 4265, 4265A, and 4265V Patient Extension Cables.

5. Failure to establish and maintain procedures to ensure that the design requirements relating to a device are appropriate and address the intended use of the device, including the needs of the user and patient, and failure to document the design input requirements, as required by 21 CFR 820.30(c).
For example:

(a) No design input requirements procedures were established for the Model 4265, 4265A, and 4265V Patient Extension Cables.

(b) There are no written design input requirements for the Model 4265, 4265A, and 4265V Patient Extension Cables.

6. Failure to establish and maintain procedures for defining and documenting design output in terms that allow an adequate evaluation of conformance to design input requirements, and failure to establish procedures that contain or make reference to acceptance criteria to ensure that those design outputs that are essential for the proper functioning of the device are identified. Failure to document design output before release, as required by 21 CFR 820.30(d). For example:

(a) Essential design outputs for the Model 4265, 4265A, and 4265V were not identified [redacted]

(b) Design output requirements were not documented, reviewed, or approved for the Model 4265, 4265A, and 4265V Patient Cables.

(c) Design output acceptance criteria were not identified for the Model 4265, 4265A, and 4265V Patient Extension Cables.

7. Failure to establish and maintain procedures to ensure that formal documented reviews of the design results are planned and conducted at appropriate stages of the device's design development, as required by 21 CFR 820.30(e). For example, design reviews were not performed for the Model 4265, 4265A, and 4265V Patient Extension Cables.

8. Failure to establish and maintain procedures to ensure that the device design is correctly translated into production specifications, as required by 21 CFR 820.30(h). For example, there is no documentation that the initial production batch of the Model 4265, 4265A, and 4265V Patient Extension Cables was manufactured in accordance with the approved design specifications.

9. Failure to validate the device design and failure to perform risk analysis. Failure to document these activities, as required by 21 CFR 820.30(g). For example, (a) No design validation was conducted for the Model 4265, 4265A, and 4265V Patient Extension Cables.

(b) Risk analysis was not performed/documented for the Model 4265, 4265A, and 4265V Patient Extension Cables.

10. Failure to establish and maintain procedures for verifying the device design, including confirming that the design output meets the design input requirements, and failure to document the results of the verification, as required by 21 CFR 820.30(f). For example, no verification activities were conducted/documented for the Model 4265, 4265A, and 4265V Patient Extension Cables.

11. Failure to establish and maintain procedures for the identification, documentation, validation or verification, review, and approval of design changes before their implementation, as required by 21 CFR 820.30(i). For example, there is no documentation relating to the modification [redacted]

12. Failure to validate a process where the results of that process cannot be fully verified by subsequent inspection and testing, as required by 21 CFR 820.75(a). For example,

(a) [redacted] has not been validated. The operator varies processing parameters as needed to produce visually acceptable parts; however testing has not been done to verify that actual molding parameters will produce products meeting anticipated use conditions.

(b) Validation of the packaging sealing process used for the Model 4250 and Model 4220 Sterile Disposable Surgical Extension Cable did not include all appropriate installation qualification requirements (e.g., sealer calibration, preventive maintenance); operational qualification (e.g., process control limits for dwell time and pressure, training action levels, worst case conditions); and performance qualification (e.g., process repeatability).

(c) Validation of the [redacted] cleaning process for the Model 4220 Sterile Disposable Surgical Extension Cable did not include testing under worst case conditions [redacted]

(d) Packaging of the Model 4250 and Model 4220 Sterile Disposable Surgical Extension Cables is done in an environmentally uncontrolled area. The packaging instruction for the Model 4220 states that the time between placing the cable in the pouch and pouch sealing should be minimized. There is no data verifying that the sterilization process will achieve the required sterility assurance level under worst case environmental conditions (e.g., maximum time interval from pouching to sealing, seasonal bioburden differences).

(e) No process validation has been conducted for the Model 4265 Universal connector soldering process.

13. Failure to establish and maintain procedures for implementing corrective and preventive action that include appropriate statistical methodology which should be employed where necessary to identify existing and potential causes of nonconforming product, or other quality problems, as required by 21 CFR 820.100(a)(1). For example,

(a) The confirmed external pacemaker failures listed in Observation #36 listed by service report number, have not been evaluated to determine if corrective or preventive action is required.

(b) Serial number [redacted] Cable Assembly [redacted] was rejected on March 12, 2002 because it "Failed Electrical Test." There is no data supporting the decision not to initiate an investigation to determine the fundamental problem.

14. Failure to implement procedures for documenting corrective and preventive actions activities, as required by 21 CFR 820.100(b). For example, the [redacted]. This has not been done since October 2000.

15. Failure to implement and record changes in methods and procedures needed to correct and prevent identified quality problems, as required by 21 CFR 820.100(a)(5). For example, Model 4265 Patient Extension Cable lot released on [redacted] contained units with a poor connection between the shrouded pin connector socket and the collet terminals. Customer complaint report [redacted] dated January 2001 states that this defect was caused by the soldering technique used and the failure to test continuity to the shrouded socket. [redacted] was not revised [redacted] to specify that the shrouded socket end of the universal connector should be tested for continuity. Retraining of soldering operators in response to the soldering defects was not documented.

16. Failure to identify the action(s) needed to correct and prevent recurrence of nonconforming product and other quality products, as required by 21 CFR 820.100(a)(3). For example:

(a) Customer Complaints Report [redacted] dated March 29, 2000 related to a complaint from [redacted] where the Model E4233 Patient Cable SN [redacted] terminal collet knob holes were found to be undersized. This unit was reportedly manufactured with terminal collet knobs which had been enlarged to prevent incompatibility between this product and Cordis temporary leads. The investigation did not identify corrective action to prevent recurrence of the circumstances leading to the release of units which had not been reworked per approved requirements. The batch record for the terminal collet knobs does not document whether the holes were enlarged.

(b) Customer Complaints Report [redacted] dated February 27, 2002 relates to a complaint from [redacted] on the Model 4265 Patient Extension Cable, SN The unit was found to have a loss of connection between the shrouded red socket and red collect terminal solder joint. The investigation did not review the batch record, in process failures, operator techniques, assess the availability of similar units, etc ., to attempt to determine the root cause of this solder joint failure.

(c) A letter dated July 16, 2001, states that patient extension cable S/N [redacted] (still within its one year warranty period) was confirmed to have developed a fault. No additional investigation or corrective action was conducted.

17. Failure to maintain complaint files and failure to implement procedures for receiving, reviewing, and evaluating complaints by a formally designated unit, as required by 21 CFR 820.198(a). For example,

(a) The customer complaints procedure [redacted] customer complaints shall be [redacted]. This was not done for the complaints identified by service report number in Item # 18 (below).

(b) No complaint file has been maintained regarding a customer complaint reporting inability to secure temporary pacing leads to the slotted section of the universal connector of the model 4265 Patient Extension Cable.

(c) There is no complaint file for a complaint received from [redacted] on 7/13/2001, concerning a defective patient extension cable, S/N [redacted]

18. Failure to establish complaint handling procedures that ensure that complaints are evaluated to determine whether the complaint represents an event which is required to be reported to FDA under part 803, Medical Device Reporting, as required by 21 CFR 820.198(a)(3). For example:

The complaint handling procedure does not provide for the evaluation of complaints subject to the MDR regulation. The following examples of complaints which were not evaluated for MDR reportability involve:

(1) external cardiac pacemakers manufactured for shipment outside the US which are also manufactured for US distribution by [redacted] or
(2) manufactured by [redacted] for worldwide distribution:

 

Model Complaint

 

SN

S. Rpt. No

(a) 4570

redacted

redacted

Sensing anomaly in both channels

(b) 3070

redacted

redacted

Ventricular stimulation anomaly

(c) 4570

redacted

redacted

Atrial output does not work

(d) 4570

redacted

redacted

Atrial output does not work

(e) 4570

redacted

redacted

No output

(f) EV 4543

redacted

redacted

Sense control problem

(g) EV 4543

redacted

redacted

0051 Does not respond in demand code

(h) EV 4543

redacted

redacted

0026 Wrong pacing rate

(i) EV 4542

redacted

redacted

0027 Fails 5 Hz sense test

19. Failure to implement instructions and procedures for performing and verifying that the servicing meets the specified requirements, as required by 21 CFR 820.200(a). For example, servicing procedure [redacted]

20. Failure to analyze service reports with appropriate statistical methodology in accordance with 820.100, as required by 21 CFR 820.200(b). For example, service reports are not analyzed to determine if corrective or preventive actions are necessary to address potential quality problems.

21. Failure to document rework and reevaluation activities in the Device History Record, as required by 21 CFR 820.90(b)(2). For example:

(a) The number of Model 4250 and 4220 disposable extension cables requiring repouching due to non-conforming seals, is not documented.

(b)The number of in-process units reworked for Model 4220 Patient Extension cables, lot [redacted] had not been documented. The operator stated on 6/26/02 that there had been "about one" unit reworked and that [redacted]. The batch start date is shown as May 22, 2002.

22. Failure to maintain records of changes to documents, as required by 21 CFR 820.40(b). For example there is no documentation supporting any changes observed in the [redacted] reviewed. For example, for the Model 4265 patient Cable Extension which added the statement: [redacted]

23. Failure to establish and maintain procedures to identify, document, evaluate, segregate and dispose of nonconforming product, as required by 21 CFR 820.90(a). For example,

(a) [redacted] There are no written instructions for segregating and disposing of rejected units. One unmarked, reportedly rejected unit from lot [redacted] was observed outside a bin being used to store the majority of the units being molded on June 24, 2002.

(b) Complaint [redacted] dated January 2001 states that all model 4265 patient extension cables were isolated and replaced. Reportedly, all cables identified with a poor connection (solder defect) between the shrouded pin connector socket and four jaw collet terminals were destroyed. There is no documentation confirming that the defective cables were destroyed.

24. Failure to establish and maintain acceptance procedures to ensure that specified requirements for in-process product are met . Failure to ensure that in-process product is controlled until the required inspection and tests or other verification activities have been completed, or necessary approvals are received, and are documented, as required by 21 CFR 820.80(c). For example:

(a) Stage [redacted] of the [redacted] for batch [redacted ] of the model 4220 disposable Cable Assembly states that [redacted]. The actual number of units inspected is not documented. [redacted] however, there was no
documentation verifying that the appropriate number of samples had already been tested .

(b) Completion of stage [redacted] for Model 4265 for PMI, [redacted] lot dated [redacted] relating to the [redacted] Seven units from this lot were reworked beginning at the previous [redacted] however, there is no documentation that these units were tested at stage

25 . Failure to establish and maintain adequate procedures for finished device acceptance to ensure that each production run, lot, or batch of finished devices meets acceptance criteria, as required by 21 CFR 820 .80(d) . For example, no quality assurance provisions have been established for confirming that production and quality requirements have been met . No QA tests have been done concerning functional and electrical requirements for the model 4250 and 4265 leads.

26 . Failure to conduct quality audits in a manner which would assure that the quality system is in compliance with the established quality system requirements and to determine the effectiveness of the quality system, as required by 21 CFR 820 .22 . For example, the firm's quality audits did not verify that the quality system is effective in fulfilling the firm's quality system objectives.

27 . Failure to evaluate and select potential contractors on their ability to meet specified requirements, including quality system requirements and to document these activities, as required by 21 CFR 820.50(a)(1). For example, there is no documentation relating to the evaluation of the individual responsible for conducting the biannual internal audits.

The law also requires under Section 519 of the Act that manufacturers and importers into the United States, of devices, establish and maintain such records, make such reports, and provide such information as the FDA by regulation reasonably requires to assure that a device is not adulterated or misbranded and to otherwise assure its safety and effectiveness. FDA promulgated under referenced Section 519, the Medical Device Reporting Regulation, 21 CFR Part 803. Our inspection revealed that your firm has not met the requirements of 21 CFR Part 803 in that your firm failed to develop, implement, and maintain, written MDR procedures, as required by 21 CFR 803.17. The failure to comply with this requirement causes your devices to be misbranded within the meaning of Section 502(t)(2) of the act .

A review of our records has also revealed that your firm has not registered, listed, or identified a U.S. agent, as required by title 21, Code of Federal Regulations, part 807, section 40 (21 CFR 807.40) for firms exporting to the United States. Any establishment within any foreign country that is engaged in the manufacture or processing of a device that is imported or offered for import into the United States must register and list such device in conformance with part 807, subpart B. Each establishment must also submit the name, address, and phone number of its United States agent as part of its initial and updated registration information. The U.S. agent must reside or maintain a place of business in the United States. The failure to comply with these requirements causes your devices to be misbranded within the meaning of Sections 502(o) and 502(t)(2) of the Act. No device may be imported or offered for import into the United States unless it is the subject of a device listing and is manufactured or processed at a registered foreign establishment.

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 closeout 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. If the causes are determined to be systems problems, you must promptly initiate permanent corrective actions.

Given the serious nature of these violations of the Act, the Cardiac Pacer Extension Cables, Pacer Analyzer Cables, and Temporary Cardiac Pacers, may be detained without physical examination upon entry into the United States (U.S.) until these violations are corrected.

In order to remove the devices from this detention, it will be necessary for you to provide a written response to the charges in this Warning Letter for our review. After we notify you that your response is adequate, we will request an establishment re-inspection at that time. As soon as the re-inspection has taken place, the implementation of your corrections has been verified, and you are notified that your corrections are adequate, your devices may resume entry into this country.

Please notify this office in writing of the specific steps you have taken to correct the noted violations, including an explanation of each step being taken to identify and make corrections to any underlying systems problems necessary to assure that similar violations will not recur. Please include any and all documentation to show that adequate correction has been achieved. In the case of future corrections, an estimated date of completion, and documentation showing plans for correction should be included with your response to this letter. Please address your response to:

Donald W. Serra, Chief
Cardiovascular and Neurological Devices Branch (HFZ-341)
Center for Device and Radiological Health
Office of Compliance
Division of Enforcement III
2098 Gaither Road
Rockville, MD 20850
USA

If you have any questions, please contact Mary Jo Hazes at the above address or at (301) 594-4648, ext. 133, or fax (301) 594-4672. You may obtain general information about all of FDA's requirements for manufacturers of medical devices by contacting our Division of Small Manufacturers, International and Consumer Assistance (DSMICA, formerly DSMA) at (800) 638-2041, or through the Internet at http://www.fda.gov.

Sincerely yours,

/S/

Philip J . Frappaolo
Acting Director
Office of Compliance
Center for Devices and Radiological Health

cc: [redacted]

.