Company: Applied Water Engineering, Inc.
Subject: CGMP/QSR/Medical Device Reporting/Adulterated
Issuer: Denver District Office
Issued: Dec. 27, 2006 Closed:
Not applicable.
Source ucm076224 Archive Code:

Applied Water Engineering, Inc. 27-Dec-06

Department of Health and Human Services

Public Health Service
Food and Drug Administration

Denver District Office
Bldg. 20-Denver Federal Center
P.O. Box 25087
6th Avenue & Kipling Street
Denver, Colorado 80225-0087
Telephone: 303-236-3000
FAX: 303-236-3551

December 27, 2006



Mr. Stephen C. Carr
Applied Water Engineering, Inc.
2759 South 300 West, Suite G
Salt Lake City, Utah 84115

Ref # DEN-07-03

Dear Mr. Carr:

During an inspection of your firm located in Salt Lake City, Utah on July 11 through July 14, 2006, our investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures the PA2000 and SPD reverse osmosis (RO) water purification systems for dialysis, and the Bicarb Mixer. 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. ยง 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 (CFR), Part 820. Significant violations include, but are not limited to, the following:

1. Failure 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, design changes were not documented or reviewed for the transformation of the older model (OFD). into the newer model known as the PA2000 [redacted] Change Order Procedure, approved [redacted] only outlines the order process for replacement parts. This procedure does not address the requirements for design changes from the OFD model to the PA2000 model. Further, there was no evidence of design validation or verification or documentation of risk analysis prior to the implementation of design changes.

2. Failure to establish and maintain a design history file (DHF) for each type of device, as required by 21 CFR 820.30(j).

For example, your firm lacked complete DHFs for both the SPD and the PA2000.

3. Failure to establish and maintain procedures for implementing corrective and preventive actions, including procedures for analyzing processes, work operations, concessions, quality audit reports, quality records, service records, complaints, returned product, and other sources of quality data to identify existing and potential causes of nonconforming product, or other quality problems, as required by 21 CFR 820.100(a)(1).

For example, your firm's procedures did not address the analysis of service repairs or defective component complaints.

4. Failure to meet servicing requirements as specified at 21 CFR 820.200.

For example, customer service calls are not being adequately documented as required by 21 CFR 820.200(d). Your firm only maintains invoice records of parts sold to a customer and replacement parts sold to remedy a problem with a device. Because your firm fails to adequately document service calls your firm is unable to determine if such calls represent an MDR reportable event that must be treated as a complaint and processed in accordance with the requirements of 21 CFR 820.198, as required by 21 CFR 820.200(c).

5. Failure to establish and maintain process control procedures that describe any process controls necessary to ensure conformance to specifications such as documented instructions, standard operating procedures (SOPs), and methods that define and control the manner of production, as required by 21 CFR 820.70(a)(1).

For example, your firm did not have any written assembly instructions or manufacturing procedures for the SPD or PA2000.

6. Failure to establish and maintain 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, a review of the acceptance activities revealed no documentation of your firm's finished device testing and there were no dates, results, or verification of completeness of DMRs associated with production testing for the SPD or PA2000. Your firm manufactured and distributed [redacted] PA2000s and [redacted] SPDs without any signature release (i .e., the Device System Test Record contains a field for "Acceptance for Sale by:" and "Date", and were both left blank).

7. Failure to document training and ensure all personnel are trained to adequately perform :their assigned responsibilities, as required by 21 CFR 820.25(b).

Your Training Documentation Procedure [redacted] states, [redacted] . However, there was no documentation indicating that the full time employee who performs the manufacturing of your firm's devices and is the author of some of the device housing diagrams has
received training.

8. Failure to establish and maintain procedures to ensure that the device history records (DHRs) for each batch, lot, or unit are maintained to demonstrate that the device is manufactured in accordance with the device master record (DMR) and the established quality system requirements of 21 CFR Part 820, as required by 21 CFR 820.184.

For example, your firm lacked documentation demonstrating that your devices were manufactured in accordance with established instructions, SOPs, or methods. In addition, your firm's DHRs lacked documentation specifying which parts were used to manufacture the PA2000 or the SPD devices in 2005 and 2006.

9. Failure to establish and maintain an adequate organizational structure to ensure that devices are designed and produced in accordance with the established quality system requirements, as required by 21 CFR 820.20(b).

For example, your firm had no documentation indicating that a management representative . has been appointed to ensure that quality system requirements will be met.

10. Failure of management with executive responsibility . to review the suitability and effectiveness of the quality system at defined intervals and with sufficient frequency according to established procedures and to document the dates and results of quality system reviews, as required by 21 CFR 820.20(c).

For example, your firm had no procedures for management review and no documentation showing that management reviews have been conducted.

11. Failure to establish and maintain procedures for quality audits and conduct such 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 .

For example, your firm had no procedures for quality audits and no documentation showing that quality audits have been conducted.

Our inspection also revealed that your SPD, PA2000 and the Bicarb Mixer devices are misbranded under section 502(t)(2) of the Act, 21 U.S.C. 352(t)(2), in that your firm failed or refused to furnish material or information respecting these devices that is required by or under section 519 of the Act,, 21 U.S.C. 360i, and 21 C.F.R. Part 803 - Medical Device Reporting (MDR) regulation. Significant deviations include, but are not limited to, the following:

1. Failure to develop, maintain, and implement written MDR procedures, as required by 21 CFR 803.1 7.

Your firm's Complaint Handling Procedure, [redacted] contains references to MDR in [redacted] places [redacted ]. However, your firm has not established a separate and complete procedure for MDR reporting and the references to MDR in [redacted] fails to meet the requirements of 21 CFR 803.17. For example, [redacted] , does not provide for effective identification of events that meet the criteria of MDR reporting. Section [redacted] of the SOP contains provisions for submitting MDRs to FDA when you become aware of an event involving death or serious injury. However, our MDR regulation indicates that manufacturers must also submit MDRs whenever they become aware of an event that reasonably suggests that their marketed device has malfunctioned and that the device or a similar device marketed by the firm would be likely to cause or contribute to a death or serious injury if the malfunction were to recur, 21 CFR 803.50.

As a device manufacturer, your firm must develop a comprehensive written MDR procedure that fully meets the requirements of 21 CFR 803.17. In addition, your firm's procedure should address other specific MDR requirements as specified in 21 CFR Part 803 including, but not limited to, the requirements relating to: investigation of MDR reportable events (21 CFR 803.50(b)(3)); five-day MDR reports (21 CFR 803.53), baseline MDR reports (21 CFR 803.55), supplemental MDR reports (21 CFR 803.56), when not to file an MDR report (21 CFR 803.22), what information to include in an MDR report, i.e. MedWatch 3500A Reporting form (21 CFR 803.52), MDR event file and record retention requirements (21 CFR 803.18), and pertinent MDR definitions that are essential to determining when an event/complaint is an MDR reportable event (21 CFR 803.3).

Our inspection also revealed that the Bicarb Mixer is adulterated under section 501(f)(1)(B) of the Act, 21 U.S.C. 351(f)(1)(B), because you do not have an approved application for premarket approval (PMA) in effect pursuant to section 515(a) of the Act, 21 U.S.C. 360e(a), or an approved application for an investigational device exemption (IDE) under section 520(g) of the Act, 21 U.S.C. 360j(g). The device is also misbranded under section 502(o) the Act, 21 U.S.C. 352(o), because you did not notify the agency of your intent to introduce the device into commercial distribution, as required by section 510(k) of the Act, 21 U.S.C. 360(k). For a device requiring premarket approval, the notification required by section 510(k) of the Act, 21 U.S.C. 360(k), is deemed satisfied when a PMA is pending before the agency, 21 CFR 807.81(b). The kind of information you need to submit in order to obtain approval or clearance for your device is described on the Internet at . The FDA will evaluate .the information you submit and decide whether your product may be
legally marketed.

Additionally, your devices are also misbranded under section 502(o) the Act, 21 U.S.C. 352(o), because they are manufactured, prepared, propagated, compounded, or processed in an establishment not duly registered under section 510 of the Act; 21 U.S.C. 360, and because the Bicarb Mixer was not included in a list required by section 510(j) of the Act, 21 U.S.C. 360(j).

You should take prompt action to correct the violation(s) addressed in this letter. Failure to promptly correct these violation(s) may result in regulatory action being initiated by the Food and Drug Administration,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 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 violation(s), or similar violation(s), 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: Food and Drug Administration, Denver District, P.O. Box 25087, Denver, CO 80225-0087, Attention: William H. Sherer, Compliance Officer. If you have any questions about the content of this letter please contact Mr: Sherer at (303) 236-3051.

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 Inspectional Observations, Form FDA 483 (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.

Sincerely yours,


B. Belinda Collins
Denver District Director