Inspections, Compliance, Enforcement, and Criminal Investigations
Clark Research and Development, Inc. 09-Apr-07
Department of Health and Human Services
| Public Health Service |
Food and Drug Administration
New Orleans District
Telephone: (615) 366-7801
April 9, 2007
WARNING LETTER No. 2007-NOL-09
Dr. William T. Clark, President
Clark Research and Development, Inc.
Number 13 Park Lane
Folsom, Louisiana 70437
Dear Dr. Clark:
During an inspection of your firm, located in Folsom, Louisiana on October 18, 2006 through November 1, 2006, an investigator from the United States Food and Drug Administration (FDA) determined your firm manufactures Clark® Biocompatible Hemoperfusion Cartridges. Under Section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), [21 United States Code (USC) 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 he structure or any function of the body.
This inspection revealed these devices are adulterated within the meaning of Section 501(h) of the Act [21 USC 351(h)], in which 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 in Title 21, Code of Federal Regulations (CFR), Part 820. We received a response letter from Michael S. Pearl, Vice President, dated November 9, 2006, concerning our investigator's observations note on the Form FDA 483, Inspectional Observations (FDA 483). We address this response below, in relation to each of the noted violations. These violations include, but are not limited to, the following:
1. You failed to validate the manufacturing process with a high degree of assurance and approve it according to established procedures where the results of the manufacturing process cannot be fully verified by subsequent inspection and test. You failed to document the validation activities and results, including the date and signature of the individual(s) approving the validation and, where appropriate, the major equipment validated, as required by 21 CFR 820.75(a).
For example, your firm's validation studies for sterilization were inadequate. The typed summary of an autoclaving process did not include the following information: a date of testing; specifications; where the testing occurred; the shelf life expiration of device after autoclaving; information regarding the equipment used for testing; and, information about the sterilization process.
Mr. Pearl's response is inadequate because it did not provide documentation of validation studies for the sterilization process. Although your firm does not sterilize the device before use, the sterilization procedure identified on the device's labeling must be validated.
2. You failed to establish and maintain procedures for the identification, documentation, validation or, where appropriate, verification, review, and approval of design changes before their implementation, as required by 21 CFR 820.30(i).
For example, there is a discrepancy between the mesh size identified in the Device Master Record (DMR) and the mesh size identified in the device history record (DHR). The DMR section entitled Device Specifications refers to the U.S. Patent, which lists the mesh as [redacted]. However, the DHR for Lot Numbers [redacted] and [redacted] lists the mesh as [redacted] The Control of Component section in the DMR does not address this design change for the mesh.
Mr. Pearl's response is inadequate because it did not provide verification or validation for this design change. It should be noted a DMR must stand on its own.
3. You failed to establish and maintain procedures for changes to a specification, method, process, or procedure and to verify or, where appropriate, validate such changes according to 21 CFR 820.75, and to document these activities before implementation to ensure conformance to specifications, as required by 21 CFR 820.70(b).
For example, you failed to validate the modified drying process listed in the DHR and to document such changes in the DMR. The drying time identified in the DMR, which makes reference to the U.S. Patent, is [redacted] Fahrenheit (F) for [redacted]. However, the DHR identifies the drying time as [redacted] F for [redacted] (e.g., Lot Numbers [redacted] and [redacted]).
Mr. Pearl's response is inadequate because it did not provide verification or validation data for the drying process modification. The response characterizes this as a record keeping issue. It should be noted a DMR must stand on it own.
4. You failed to establish and maintain procedures to ensure manufacturing equipment is routinely calibrated, inspected, checked, and maintained, as required by 21 CFR 820.72(a).
For example, you had no records to document the calibration of the cartridge sealer, oven thermometers, or timing devices used to dry particles when manufacturing the hemoperfusion device.
Mr. Pearl's response is inadequate because it did not provide documentation of calibration of the manufacturing equipment.
5. Failure of the DMR to include, or refer to, the location of production process specifications, including the appropriate equipment specifications and production procedures, as required by 21 CFR 820.181(b).
For example, the DMR does not document updated specification changes listed in the DHR. Although this was not included in the FDA 483 issued to you on November 1, 2006, we request you address this issue in your response to this Warning Letter.
Our inspection also revealed the Clark® Biocompatible Hemoperfusion Cartridges are misbranded under Section 502(t)(2) of the Act, [21 USC 352(t)(2)], because your firm failed or refused to furnish material or information respecting the devices as required by Section 519 of the Act, [21 USC 360i], and 21 CFR Part 803 - Medical Device Reporting (MDR) regulation. Significant deviations include, but are not limited to, the following:
You failed to develop, maintain and implement written MDR procedures, as required by 21 CFR 803.17. For example, your firm does not have adequate written MDR procedures for the hemoperfusion cartridge. The "Complaint Report Form" does not address all of the requirements in 21 CFR 803.17.
Mr. Pearl's response is inadequate because your firm's "Complaint Report Form" does not satisfy all of the requirements in 21 CFR 803.17, including device malfunction reporting; baseline reporting; supplemental reporting; and, serious injury reporting.
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 FDA 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 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 within 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 timeframe for implementation of those corrections. If corrective action cannot be completed within 15 working days, state the reason for the delay and the time when the correction will be completed.
Your response should be sent to the U.S. Food and Drug Administration, Attention: Kari L. Batey, Compliance Officer at the above address. If you have any questions about the content of this letter, please contact Ms. Batey at (615) 366-7808.
Finally, you should know 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 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.
H. Tyler Thornburg
New Orleans District
Enclosure: Form FDA 483
cc: Michael S. Pearl
Clark Research and Development, Inc.
Number 13 Park Lane
Folsom, LA 70437