Inspections, Compliance, Enforcement, and Criminal Investigations
Lydall, Inc. 27-May-05
Department of Health and Human Services
Public Health Service
Atlanta District Office
May 27, 2005
VIA FEDERAL EXPRESS
David Freeman, President & CEO
One Colonial Rd.
Manchester, CT 06045-0151
Dear Mr. Freeman:
During an inspection of Charter Medical Limited located at 3948-A West Point Blvd., Winston-Salem, NC on January 6 through 25, 2005, our investigators determined that your firm is a manufacturer of various blood administration sets, plasma/fluid transfer sets, blood transfer bags, and neonatal/pediatric aliquot systems. These products are devices as defined by Section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C 321(h).
The inspection revealed that the referenced 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 conformance with the Current Good Manufacturing Practice (CGMP) requirements of the Quality System (QS) Regulation for medical devices, as specified in Title 21 Code of Federal Regulations (21 CFR), Part 820. The inspection also revealed that several of your devices are misbranded within the meaning of Section 502(o) of the Act. At the close of the inspection, the investigators issued a Form FDA 483 (copy enclosed) to Ms. Lisa Krallis-Nixon, General Manager, which delineated a number of significant QS inspectional observations. The violation list below includes some of the most significant of those observations, as well as the misbranding violation referenced above:
1. Failure to validate with a high degree of assurance and to approve according to established procedures, the results of a process that cannot be fully verified by subsequent inspection and test, as required by 21 CFR 820.75(a), (b). (FDA 483 item #1). Specifically,
a. Ethylene oxide (EtO) sterilization:
i. Your original 1993 ethylene oxide (EtO) sterilization validation had product sterility failures, positive Biological Indicator (BI) spore strips, and inoculated product failures. Although these failures were attributed to laboratory contaminants, laboratory reports were not available for the investigation of these failures.
ii. Your 2001 EtO revalidation does not include evidence that the validation results were reviewed and no validation summary was available.
iii. Your most recent EtO revalidation conducted in February of 2003 in [redacted] had 5 external positive BIs and 13 internal positive BIs during the half-cycle run. Your firm did not review or investigate those positive BIs, and therefore, did not validate the sterilization procedure with a high degree of assurance. Furthermore, your own SOP, "Validation Protocol EtO. 0592, Rev-C," requires your firm to make a technical judgment to accept or reject the validation study with input from the [redacted] and [redacted] technical staffs, which your firm did not do. Therefore, Charter Medical failed to approve the sterilization validation according to established procedures.
b. Gamma sterilization
i. Your 1997 gamima validation package is incomplete in that it consists of a single protocol and no other documentation.
ii. Quarterly dose audits for gamma sterilization were not performed between February 2003 and January 2005, even though your procedure, Gamma Sterilization (Document No: QS-235), states that quarterly dose audits are required.
2. Failure to review and evaluate a process and perform revalidations where appropriate when changes or process deviations occur, as required by 21 CFR 820.75 (c). (FDA 483 item #2) Specifically,
a When your manufacturing process was relocated to North Carolina, the Et0 sterilization process was not revalidated. (FDA 483 item # 1.c).
b. There was no documentation or formal review of the sterilization process when a new contractor was hired to perform gamma sterilization,
3. Failure of management with executive responsibility to establish its policy and objectives for, and commitment to, quality and to ensure that quality policy is understood, implemented, and maintained at all levels of the organization, as required by 21 CFR 820.20. (FDA 483 item #3) Specifically,
a. Your firm's management has not ensured effective routine sterilization of neonatal syringe sets, blood administration sets, plasma transfer sets, blood transfer bags, and other distributed medical devices,
b. Your firm's management was unaware that the sterilization processes were not adequately monitored, in that the quarterly dose audits for gamma sterilization were not performed, as required by your procedure, Gamma Sterilization (Document No:QS-235), and the positive BI results in your EtO half cycle revalidation were not investigated.
c. Your firm's management has not performed formal reviews of quality processes and procedures, such as procedures for evaluating environmental monitoring data, for product bioburden activities, and for Quality Control equipment calibrations. 21 CFR 820.20(c).
4. Failure to develop, conduct, control, and monitor production processes to ensure that a device conforms to its specifications, as required by 21 CFR 820.70 (a). (FDA 483 item #4) Specifically,
a. You did not have any data to substantiate the validity of the External Monitoring Systems (EMS), which are used in routine EtO processing.
b. The procedure for the preparation of External Monitoring Systems, Preparation of Biological Indicator for EtO Sterilization Work Instructions (Document No: QS-QI-215), did not reflect the actual method described in the validation protocol. In addition your procedures governing EtO sterilization were not comprehensive in that they did not address all steps in the process.
c. There is no documentation to show product line extensions have been formally evaluated for approval into the EtO or gamma processing cycles. Specific instructions, indicating which sterilization method was to be used for each of the various products you manufacture were unclear.
5. Failure to establish and maintain procedures to adequately control environmental conditions, as required by 21 CFR 820.70(c). (FDA 483 item #6) Specifically,
a The new [redacted] Monitoring System was installed in April 2004; however, your firm neither performed installation (operation qualification), both of which are necessary to assure that the system was functioning properly and according to specifications.
b. Environmental action levels for the Air Sampler test for microbes exceeded established action limits, but were not investigated on 6/25/04 ;8/20/04; 9/10/04 and 9/20/04. Your firm did not have detailed instructions for addressing alert and action levels in the controlled area.
6. Failure to conduct quality audits to 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. (FDA 483 item #7). Specifically, ten of twenty-four internal audits on the 2004 audit schedule were not completed.
7. Failure to establish and maintain procedures to ensure that the device design is correctly translated into production, as required by 21 CFR 820.30 (h). (FDA 483 item #l9) Specifically, your Design Control Procedure (Document No: DES-500) did not address design transfer.
8. Failure to perform risk analysis, where appropriate, as required by 21 CFR 820.30(g). (FDA 483 item #20) Specifically, risk analysis was not performed for design project [redacted] "Bonding to Drip Chamber".
9. Your devices, Albumin IV Administration Set (K791672A), Transfer Pack (BK960043), and Transfer Bags (K802671C, and K791673), are misbranded under section 502(o) of the Act, Specifically, you labeled these as Blood Administration Sets, and Platelet Sampling Devices, respectively, without providing FDA with notice or other information regarding the new intended uses of the devices, as required by section 510(k) and 21 CFR 807.81(a)(3)(ii). We remind you that until FDA has evaluated these devices and issued a 510(k) for their new intended uses, you may not distribute these products in interstate commerce labeled as indicated for the new intended uses.
We have reviewed your response to FDA Form 483, dated February 11, 2005, and the accompanying attachments. Except for your response to FDA Form 483 item #b.c, your responses appear adequate on their face. It is your responsibility to implement all of your proposed corrections, ensuring the corrections accomplish the goals they must achieve, and are sufficient to bring your firm into full compliance. If they do not, it is your responsibility to ensure that additional corrective and preventive actions are implemented that are sufficient. As to your response to FDA Form 483 item #6.c -- your failure to perform an installation qualification (IQ) of the [redacted] Monitoring System -- in addition to acknowledging that an IQ should have been performed, you should also evaluate the installation through a post-installation, documented calibration (Operation Qualification), and you should establish a schedule for routine calibration and preventive maintenance of the system.
Finally, in light of the evidence discussed in violation #9 above that your firm has marketed other devices without proper 510(k) clearance, we have concerns that your firm may be marketing other unapproved devices. For that reason, we ask that you review all devices that your firm currently markets, and in the response to this letter, provide a chart listing each device, the indications for which it is labeled and promoted, and the 510(k) clearance for each device and each intended use.
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 causes of the violations identified by the FDA. You also must promptly initiate permanent corrective and preventive actions on 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 considering the award of contracts. Additionally, FDA will not approve any applications for premarket approval (PMAs) for Class III devices to which the Quality System regulation deficiencies are reasonably related until the violations have been corrected. Also, no request for Certificates For Export will be approved until the violations related to the subject devices have been corrected.
You should take prompt action to correct these violations. Failure to promptly correct these violations may result in regulatory action being initiated by FDA without further notice. These actions include, but are not limited to, actions for seizure, injunctions, and/or civil money penalties.
Please provide this office in writing within fifteen (15) working days of receipt of this letter a report of the specific steps you have taken, or will take, to identify and correct the noted violations, including an explanation of each step being taken to ensure that similar violations will not recur. To the extent that you have implemented the corrective actions promised in your response to the FDA Form 483, please state when the corrective actions were fully implemented, when they were validated and the results of the validation (if applicable), and what changes you made, if any, to the corrective actions to ensure that they are effective. If corrective actions cannot be completed within fifteen (15) working days, state the reason for the delay and the time within which the corrections will be completed. Please send your response to the attention of Serene N. Ackall, Compliance Officer at the address noted in the letterhead. If you have any questions about this letter, you can contact Serene Ackall at 404-253-1296.
Mary Woleske, Director