Inspections, Compliance, Enforcement, and Criminal Investigations
DeRoyal Industries, Inc. 14-Jan-04
Department of Health and Human Services
Public Health Service
New Orleans District
January 14, 2004
Warning Letter No. 2004-NOL-11
VIA FEDERAL EXPRESS
Pete DeBusk, President and CEO
DeRoyal Industries Inc.
200 DeBusk Lane
Powell, Tennessee 37849
Dear Mr. DeBusk:
During an inspection of your establishment, located at 1211 Highway 33 South and 1595 Highway 33 South, New Tazewell, Tennessee, on November 20 - 21, December 2-3, 5 and 9, 2003, our investigator determined that your Multidex Wound Dressing Products (powder and gel) are adulterated within the meaning of Section 501(h) the Act [21 USC 351(h)], in that the methods used in, or the facilities or controls used for the devices manufacture, packing, storage, or installation are not in conformity with applicable Current Good Manufacturing Practice (CGMP) requirements, which are set forth in the Quality System Regulation (QSR) for medical devices as specified in Title 21, Code of Federal Regulations (CFR), Part 820.
The inspection revealed the following violations:
1. Your firms sampling plans are not based on a valid statistical rationale
as required by 21 CFR 820.250(b). Specifically, the bioburden samples used for
validation of the current sterilization cycle for the Multidex were collected
during a period of 3 days (for powder) and 7 days (for gel) without a major
equipment cleaning when, according to your records, production runs have lasted
as long as 1 month for powders and approximately 1 1/2 months
for gels before a major equipment cleaning.
2. Your firm failed to establish and maintain procedures for implementing corrective and preventive action, including requirements for identifying the action(s) needed to correct and prevent recurrence of non-conforming product and other quality problems as required by 21 CFR 820.100(a)(3). Specifically, you did not take appropriate actions for product on the market or in house when a dose audit failure occurred.
3. Your firm failed to conduct process validation as required by 21 CFR 820.75.
a. Process validation activities and results have not been documented fully
as required by 21 CFR 820.75(a). Specifically, records were not available to
show that the Burst Test on lot 31255 was performed at the maximum sterilization
b. There is no documentation of monitoring and control methods and data for a validated process as required by 21 CFR 820.75(b)(2). Specifically, you do not have all information regarding dose mapping, load patterns, and dosimeter locations, currently in use by your contract sterilizer.
c. There is no documentation of the revalidation of a process conducted in response to changes or process deviations as required by 21 CFR 820.75(c). Specifically, your firm failed to document approval to increase the maximum sterilization dose from [redacted] to [redacted] kGy for Multidex and a lack of Multidex bioburden limits even though at least two Standard Operating Procedures (SOPS) require such limits.
4. Your firm failed to establish and maintain design controls procedures as required by 21 CFR 820.30.
a. The design plan does not describe the design and development activities
and does not identify or describe the interfaces with different groups or activities
as required by 21 CFR 820.30(b). Specifically, the Multidex Design Plan 1999/40/001
does not describe any specific activities to be performed.
b. Design input requirements were not documented as required by 21 CFR 820.30(c).
Specifically, design control records were frequently undated and/or lacked references,
such as lot number identifying the nature of the information on the document.
c. Design output procedures do not ensure that those design outputs essential for the proper functioning of the device are not identified as required by 21 CFR 820.30(d). Specifically, the Multidex Design History File did not include essential outputs, such as finished product specifications, bill of materials, pyrogen test results, and complete equipment validation data.
d. Design verification did not confirm that the design output meets the design input requirements as required by 21 CFR 820.30(f). Specifically, design verification was reportedly performed, but did not include documented reconciliation of design inputs vs. design outputs.
e. Design validation was not performed under defined operating conditions on initial production units, lots, or batches, or their equivalents, and the results of the design validation were not documented in the design history file as required by 21 CFR 820.30(g). Specifically, validation studies were not performed per protocol and you failed to adequately review validation data that was performed.
f. Procedures were not established and maintained to ensure that the device
design was correctly translated into production specifications as required by
21 CFR 820.30(h). Specifically, your firm failed to document training as a requirement
and failed to document that training was performed during the design project..
5. Your firm failed to establish and maintain procedures for acceptance of
finished devices as required by 21 CFR 820.80(d). Specifically, for Multidex
Powder, no acceptance activities are performed other than record review and,
for Multidex Gel, an assay for ascorbic acid was not performed as required by
6. Your firms schedules for the adjustment, cleaning, and other maintenance of equipment were not established as required by 21 CFR 820.70(g)(1). Specifically, Multidex cleaning procedures do not describe minor cleaning and major cleaning frequencies.
7. Your firms procedures for control and distribution of finished devices failed to ensure that expired or deteriorated devices are not distributed as required by 21 CFR 820.160(a). Specifically, aging studies designed to justify Multidex expiry dates revealed protocol deficiencies, failure to meet acceptance criteria, and failure to perform specific tests at specified intervals. There were no formal conclusions drawn about the studies, and the expiry dates were not approved formally. The expiry date for Multidex Powder was 2 years, but was changed to 5 years, with no documented approval for the change.
8. Your firm failed to establish and maintain procedures to ensure that all purchased or otherwise received product and service conform to specified requirements as required by 21 CFR 820.50. Specifically, procedures for receiving components fructose and glycerin did not provide assurance that they would meet USP specifications. Different written procedures for receiving labels and labeling contained contradictory requirements and sampling/inspection procedures always did not comply with written procedures.
9. Your firms device history record was not maintained to demonstrate
that the device is manufactured in accordance with the device master record
as required by 21 CFR 820.184. Specifically, the device history record for Multidex
lot 228865 was incomplete in that several line entries were blank However, final
review of the record was performed, and the lot was released.
10. Your firm conducted incomplete complaint procedures as required by 21 CFR 820.198.
a. Complaints involving the possible failure of a device to meet any of its specifications were not processed in a uniform and timely manner and were not investigated as required by 21 CFR 820.198(a) & (c). Specifically, the complaint handling SOP requires an investigation within [redacted] days. Ten of 14 complaints reviewed, when the complaint was more than [redacted] days old (up to [redacted] months old), did not contain the results of an investigation, or justification for not performing an investigation.
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 applicable requirement of the Act and of FDA regulations. The specific violations noted in this letter and the Form FDA 483 issued at the conclusion of the inspection may be symptomatic of serious underlying problems in your establishments Quality System. You are responsible for investigating and determining the cause of the violations identified by the U.S. Food and Drug Administration (FDA).
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, no requests for Certificates to Foreign Governments will be approved until the violations related to the subject device 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 FDA without further notice. There actions include, but are not limited to, seizure, injunction, and/or civil penalties.
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 each step being taken to identify and make corrections
to any underlying system problems necessary to assure that similar violations
will not occur.
If corrective action cannot be completed within fifteen (15) working days,
please state the reason for the delay and the time within which the corrections
will be completed.
Your reply should be directed to the attention of Joseph E. Hayes, Compliance Officer, Food and Drug Administration, 297 Pius Park Boulevard, Nashville, Tennessee 37217.
Patricia K. Schafer
Acting District Director
New Orleans District