Inspections, Compliance, Enforcement, and Criminal Investigations
Nurse Assist, Inc. 09-Nov-07
Department of Health and Human Services
Public Health Service
November 9, 2007
RETURNED RECEIPT REQUESTED
Mr. Kevin W. Kile, President and CFO
Nurse Assist, Inc.
3400 Northern Cross Blvd.
Fort Worth, Texas 76137-3600
Dear Mr. Kile:
During an inspection of your firm located at the above-referenced address in Fort Worth, Texas on August 21 through September 12, 2007, an investigator from the United States Food and Drug Administration (FDA or Agency) determined that your firm manufactures a sterile water and sterile normal saline solution of 0.9% sodium chloride that were cleared for device irrigation and not for injection as stated in your firm's 510(k) K003402 and K973734. 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 any 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 (C.F.R.), Part 820.
The FDA investigator issued the observations, which are listed on the Form FDA 483 (List of Inspectional Observations), to you at the end of the inspection on September 12, 2007. The FDA 483 was annotated and re-issued to you on September 14, 2007, to document your verbal promises of corrections. The violations include, but are not limited to, the following:
Quality System Violations
1. 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 and the needs of the user and patient, and that design input procedures include a mechanism for addressing incomplete, ambiguous, or conflicting requirements, and that the design input requirements shall be reviewed, approved, and documented by designated individual(s), as required by 21 C.F.R. § 820.30(c). This issue was not included in the FDA483 that was issued to you on September 12, 2007. However, the FDA investigator discussed it with you near the end of the inspection. Specifically, your firm did not adequately review the devices' intended use on the device labeling and labels for accuracy in order to prevent potentially incorrect use of the devices by users or patients. For example:
a. The Agency cleared your firm's Premarket Notification (510(k)) submissions, K003402 and K973734, for your sterile water and sterile normal saline to be used for irrigation of medical devices. The current foil lid labels on your devices state "Caution: For irrigation only not for injection." The ambiguous word "irrigation" alone could cause the devices to be interpreted and used for wound irrigation, cleansing, or other uses rather than limited to irrigation of medical devices.
b. Your firm places a National Drug Code (NDC) number on the foil lid labels of the 120-ml cups of sterile water and saline, and the white stick-on labels of the 100ml and 250-ml bottles of sterile water and saline. Each unique NDC number is an identifier assigned for each product intended as a human drug. Placing the NDC number on the device label could cause the devices to be interpreted or incorrectly used as human drugs. Your firm is advised that the Agency cleared your sterile water and sterile normal saline as devices and not drugs as stated in K003402 and K973734.
2. Failure to establish and maintain adequate procedures for validating the device design to ensure that that the device conforms to user needs and intended uses, that acceptance criteria are established prior to performing validation activities, that design testing is conducted under actual or simulated use conditions, and that the design testing results are documented, as required by 21 C.F.R. § 820.30(g). This issue was not included in the FDA 483 that was issued to you on September 12, 2007, but the FDA investigator discussed it with you near the end of the inspection.
Your firm promotes your "USP sterile solutions" for "wound care and irrigation," a modified intended use of the devices, on your firm's website at http://www.rnplus.com without conducting an adequate design risk analysis and design validation and documenting their results to ensure that the devices conform to defined user needs and intended uses. During the inspection, your firm's Vice President of Operations verbally stated that your firm had no design history file or design control records for the existing sterile water and sterile normal saline nor obtained their design control records from Welcon when your firm bought their 510(k)s, products, and manufacturing equipment in 2005.
During your discussion with the FDA investigator, you stated that your firm will be "re-constructing" or "re-engineering" the device design control records.
3. Failure to adequately validate manufacturing processes with a high degree of assurance, approve, and document the results of the validation activities to ensure that product specifications can be consistently met, as required by 21 C.F.R. § 820.75(a). FDA 483, Item 1. Your firm did not adequately validate or revalidate the fluid and packaging (heat seal) systems after your firm acquired them from Welcon and moved them to your facility. For example:
a. Your firm's validation of the Welcon's fluid system did not attach or prepare a validation summary report to ensure that all validation elements are completed as per Section 6.3 of the "Validation Protocol Fluid Instruction, No. W-7.1-3, Revision A," dated 5/24/05.
b. Your firm relied on the existing Welcon's "Environmental Validation Record Fluid, No. F7.1-3.2, Revision A, dated 5/24/05" intended for Welcon's manufacturing facility without evaluating the procedures to determine whether or not they meet your specified environmental conditions for your Fort Worth, Texas manufacturing facility. For example, Section 5.3 of this validation record documented "bioburden level is evaluated regularly" without attaching and explaining your manufacturing facility's bioburden test results.
c. Your firm relied on the existing Welcon's "Equipment Validation Record Fluid, No. F-7.1-3.3, Revision A, dated 5/24/05" without establishing specific acceptance criteria other than the "Pass" or "Fail" criteria and documenting the actual test results to ensure the proper installation of each component of the Welcon's fluid system, water/saline filling stations, and associated test equipment.
d. Installation qualification parameters of the individual components of the fluid system were not clearly defined in that your validation protocol did not state the expected operation parameters for the [redacted] filter, [redacted]
e. Your firm's 5124105 validation of the Welcon's fluid system did not define the pre-existing contaminants in the feed water or seasonal variations of the feed water at the Fort Worth, Texas manufacturing facility.
f. Your firm's 5/24/05 validation of the fluid system did not address the use of the [redacted] treatment (sanitization) of the water loops and provide adequate documentation of the bioburden test results before and after the use of the [redacted] treatment. You provided the "[redacted] Treatment of DI Water Loop" procedure that was not approved and dated by designated individual(s).
g. Your firm's "Cup Line Sealing Process Validation Test Protocol," approval dated 8/25/06, did not specify possible worst case conditions and operating heat seal parameters (e.g., conveyor speeds, upper and lower limits of the pressure, time, and temperature). Additionally, Attachment 1 of this test protocol did not document the specific seal pressure and time settings for the water cups being sealed and leak tested.
h. Your firm's heat seal process has not been validated for the 100-ml bottle size of saline and 250-ml bottle size of saline and water. Your firm's heat seal validation for the 100-ml bottle size of water did not explain possible worst case conditions and operating heal seal parameters.
4. Failure to establish and maintain procedures to prevent contamination of equipment or product by substances that could reasonably be expected to have an adverse effect on product quality, as required by 21 C.F.R. § 820.70(e). FDA 483, Item 8.
a. An air return (intake) grid in the fluid production room was observed to be soiled on 8/29/07 during the inspection.
b. The "[redacted] Treatment of DI Water Loop" procedure did not define intervals for sanitizing the water loop of the fluid system.
c. The bottom of the filling tank containing purified water or saline was observed to be rusty and leaking.
d. The drain hose connecting from the saline reservoir to the drain container did not have an air gap to prevent potential back siphonage of wasted water.
e. Your firm did not have procedures that define the requirements and intervals for the adjustment, cleaning, or replacement of the individual components of the fluid system, e.g., the [redacted] filter, [redacted] materials of the deionization tanks, [redacted] etc., based on data gathered during your 5/24/05 validation of the fluid system.
5. Failure to develop, conduct, control, and maintain production processes to ensure that a device conforms to its specifications, as required by 21 C.F.R. § 820.70(a). FDA 483, Item 7. Your firm's production process control procedures were not implemented. Specifically, your firm did not perform the pouch peel test using the peel strength instrument to check the seal integrity of the foil lid on the sterile water and saline bottles or cups, as required by Procedure WI020 "Post-Sterilization Product Test and Release," approval dated 8/16/05.
6. Failure to document corrective and preventive action activities and their results, including investigations of causes of nonconformities, the verification or validation of corrective actions, implementation of corrective and preventive actions, and dissemination of information about quality problems or nonconforming product to responsible parties, as required by 21 C.F.R. § 820.100(b). FDA 483, Item 3.
a. Your firm's action to change the maintenance company for your fluid system was not documented in the CAPA record, as required by SOP QP033.
b. Your firm's action to "scrap the product" and "cartons" due to "dirt in carton" found during incoming inspections was not documented in the CAPA record, as required by SOP QP033. Your firm also did not update the specification or drawing for Part # 450 (160-ml bottles) and Part # 451 (screw caps) to reflect your added inspection criteria.
c. Your firm's action to increase the frequency of cleaning/sanitation of the fluid system, as a result of bacterial contamination of two lots on 11/14/05, was not incorporated into the "W1060 Cup Line [redacted] Preventive Maintenance" procedure.
7. Failure to establish and maintain procedures for identifying training needs and to ensure that all personnel are trained to adequately perform their assigned responsibilities and that their training is documented, as required by 21 C.F.R. § 820.25(b). FDA 483, Item 5. Specifically, three production employees were not trained on several specific manufacturing procedures.
8. Failure to maintain device master records (DMR) that include or refer to the location of, device specifications, production process procedures and specifications, quality assurance procedures and specifications, and packaging and labeling procedures, and a failure to ensure that each DMR is prepared and approved in accordance with 21 C.F.R. § 820.40, as required by 21 C.F.R. § 820.181. FDA 483 Item 1(e) and 6. Specifically, your firm's drawing of the fluid system did not show the entire return loop for saline solutions, and the drawing of the water loop and saline loop was not reviewed, signed, and dated by designated individual(s).
9. Failure to ensure that sampling plans, when used, are written and established and based on valid statistical rationale, as required by 21 C.F.R. § 820.250(b). FDA 483, Item 4. Specifically, the sampling plans for the referenced bioburden, endotoxin, and heavy metal testing were based on arbitrary sample quantities.
10. Failure to establish and maintain procedures for quality audits and conduct such audits to assure that the quality system is in compliance with established quality system requirements and to determine the effectiveness of the quality system, as required by 21 C.F.R. § 820.22. FDA 483, Item 9. For example, your firm has conducted ineffective quality audits in that the Agency identified significant deviations as listed on the FDA483 and this warning letter.
Your firm is advised to consult with the Division of Dental, Infection Control, and General Hospital Devices Branch of the Office of Device Evaluation of CDRH to determine whether or not your firm must submit a premarket notification 510(k) should your firm wish to market the current sterile water and sterile normal saline for wound care or wound irrigation. Two of the 510(k)s that your firm acquired from Welcon; K003402 and K973734, were cleared for device irrigation only. We request that you respond to this issue in your firm's response to this warning letter.
Responding to This Warning 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 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 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 (21 C.F.R. Part 820) 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 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 Thao Ta, Compliance Officer, Dallas District Office, Food and Drug Administration, HFR-SW140, 4040 N. Central Expressway, Suite 300, Dallas, Texas 75204. If you have any questions about the content of this letter, please contact Mr. Ta at 214-253-5217.
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 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.
Acting Dallas District Director