Inspections, Compliance, Enforcement, and Criminal Investigations
GE Infrastructure, Water & Process Technologies 28-Sep-07
Department of Health and Human Services
Public Health Service
September 28, 2007
RETURNED RECEIPT REQUESTED
Mr. Jeffery R. Garwood, President and CEO
GE Infrastructure, Water & Process Technologies
436 Someron Road
Trevose, Pennsylvania 19053-6783
Dear Mr. Garwood:
During an inspection of your firm, GE Ionics, Inc., located at 4740 Bronze Way, Dallas, Texas 75236 on July 18 through August 16, 2007, an investigator from the United States Food and Drug Administration (FDA or Agency) determined that your firm manufactures water purification tanks consisting of mixed-bed deionization (DI) tanks and/or carbon tanks that are used to provide treated water for use in hemodialysis treatment. 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 (CFR), Part 820.
The FDA investigator issued the observations, which are listed on the Form FDA 483 (Inspectional Observations), to your firm's designated manager at the end of the inspection on August 16, 2007. The designated manager verbally promised corrections. However, neither GE Infrastructure, Water & Process Technologies nor GE Ionics, Inc. has responded in writing to the inspectional observations. The Agency requests that you submit a written response to adequately address ail the inspectional observations and specific items cited in this Warning Letter, provide a timeframe for completing corrective actions, and conduct a complete internal quality audit to address significant gaps in your firm's quality system. FDA follow-up inspections will be necessary to assure that your firm's corrections are adequate. These violations include, but are not limited to, the following:
Quality System Violations
1. Failure to establish and maintain procedures to control the design of the device in order to ensure that specified design requirements and all of the requirements of 21 CFR § 820.30(b) through (j) are met, as required by 21 CFR § 820.30(a). FDA 483 Item 1. For example, your firm's on-site manager verbally stated that your firm did not have any written design control procedures and design records which document the design development process or design changes in the mixed-bed deionization (DI) tanks and carbon tanks that are manufactured for hemodialysis use. The on-site manager further stated that in 2003, your firm switched from using [redacted] resins to [redacted] resins for manufacturing the water purification tanks but that this verbal design change was not documented.
2. Failure to maintain device master records (DMR) to 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 specifications, to ensure that each DMR is prepared and approved in accordance with 21 CFR § 820.40, as required by 21 CFR § 820.181. FDA 483 Items 2 and 6. For example, your firm does not have:
a. Adequate written specifications for the empty tanks, resin materials, carbon materials, and resin regeneration process for manufacturing the water purification tanks for hemodialysis use. For instance, your firm's on-site manager stated to use the [redacted] of the cation and anion resins for hemodialysis use, but this specification was not documented. Your firm provided the investigator a simple hand written "Product/Manufacture Flow Diagram" that was not dated and approved by designated individual(s) and did not contain complete engineering descriptions and specifications of the resin [redacted] equipment. Your firm provided the investigator the [redacted] material safety data sheets (MSDS) that do not document whether the materials were tested and approved for use in hemodialysis treatment, or whether their product water complied with any recognized national/international standards intended for water treatment equipment used for dialysis. The inspection also documented that your firm manufactured water purification tanks intended for industrial uses in power plants and [redacted]
b. Adequate labeling procedures for documenting specific product information on the tank labels, where and how the labels are to be applied on the resin and carbon tanks, and how the labels are inspected for accuracy. The information provided by your on-site manager and recorded on the tank label is inconsistent. For example, the on-site manager verbally stated that your firm only used [redacted] resins, not [redacted] resins, for hemodialysis use. However, the tank label (tag) documented that the resin tank's status was to be identified as either "Medical Device," "Exhausted," "In use," or "[redacted]"
3. Failure to establish and maintain procedures to ensure that the device history records (DHR) for each batch, lot, or unit are maintained to demonstrate that the device is manufactured in accordance with the device master record, as required by 21 CFR § 820.184. FDA 483 Item 3. Specifically, your firm did not have complete DHR's for documenting tank filling operations, tank acceptance records (e.g., resistivity test results of resin tanks, test results of carbon tanks, test dates, review and approval of the test results prior to distribution), percentage of mixed resins, the dates of tank filling, or the tank quantity filled with the resin and carbon materials and installed at the dialysis sites.
4. Failure to establish and maintain adequate procedures for finished device acceptance to ensure that each production run, lot, or batch of finished devices meets acceptance criteria and that acceptance activities are documented and reviewed prior to releasing the devices for distribution, as required by 21 CFR § 820.80(d) and 820.80(e). FDA 483 Item 5. Specifically, your on-site manager stated that your firm conducted resistivity testing of the mixed-bed resin tanks prior to their installation but had not maintained their resistivity test results. Your firm also did not have written acceptance procedures for the verifications, inspections, or tests of the resin-filled and carbon tanks.
5. Failure to establish and maintain procedures, including inspections, tests, or verification activities, for incoming product and for documenting the acceptance or rejection of the incoming product, as required by 21 CFR § 820.80(b). FDA 483 Item 7. For example, your firm did neither conduct and document incoming acceptance activities nor have written acceptance procedures for verifications, inspections, tests, acceptance criteria, and documenting acceptance test results on the incoming products which include [redacted] or [redacted] cation and anion resins, carbon, empty tanks, and exhausted resin/carbon-filled tanks that were returned from the dialysis sites.
6. Failure to establish and maintain adequate process control procedures that describe any process controls necessary to ensure that a device conforms to its specifications, as required by 21 CFR § 820.70(a). FDA 483 Item 4.
Your firm's production procedure "SOP-01-1001 Preparing Mixed Bed Ion Exchange Tanks," issue dated 7/7/07, is either incomplete or deficient. For example:
a. The referenced procedure does not require cleaning or sanitizing of returned or new tanks prior to filling them with the carbon/resin materials.
b. The referenced procedure does not specifically indicate that your firm is to use only [redacted] DI resins and carbon intended for hemodialysis as your on-site manager verbally stated during the inspection.
c. The referenced procedure does not indicate specific production process specifications intended for hemodialysis use and industrial use in order to prevent potential mixups of their production processes and cross product contamination.
7. Failure to establish and maintain procedures to ensure that mixups, damage, deterioration, contamination, or other adverse effects to product do not occur during handling, as required by 21 CFR § 820.140. FDA 483 Items 8 and 9. For example, when an employee received exhausted deionization/carbon tanks returned from either a dialysis facility or an industrial facility and emptied used resins or carbon into a bag, there were no procedures requiring their empty tanks and resins/carbon to be separated in order to prevent the possible use of exhausted or incorrect materials for hemodialysis.
8. Failure to establish and maintain procedures for controlling storage areas and stock rooms for product to prevent mixups, damage, deterioration, contamination, or other adverse effect pending use or distribution to ensure that no obsolete, rejected, or deteriorated product is used or distributed, as required by 21 CFR § 820.150(a). FDA 483 Items 8 and 9. Specifically, your firm did not have written procedures that require and control separate storage area(s) for receiving and storing water purification tanks and their content materials (resins or carbon) intended for hemodialysis use and industrial use.
9. Failure to establish and maintain adequate installation and inspection instructions, and where appropriate test procedures, to ensure proper installation so that the device will perform as intended after installation, as required by 21 CFR § 820.170(a), and to document the results of inspection or testing, as required by 21 CFR § 820.170(b). FDA 483 Item 10. Specifically, there were no written installation instructions or procedures that describe how your firm's employees are to install the water purification tanks into a hospital dialysis system, what inspection or testing is to be conducted during or after installation, and how inspection or test results are to be documented to demonstrate the proper installation.
10. 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 CFR § 820.25(b). FDA 483 Item 11. Specifically, there is no training documentation that your firm's employees have received training in the receiving, handling, filling, testing, and installation of the water purification tanks intended for hemodialysis.
11. 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 CFR § 820.22. FDA 483 Item 12. For example, your firm has not conducted any internal quality audits of its quality system in order to assure your firm's compliance with the quality system regulation.
Medical Device Reporting (MDR) Violation
Our inspection also revealed that your firm's water purification tanks (resin and carbon tanks) marketed, distributed, and installed for use in hemodialysis 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 the devices that is required by or under by Section 519 of the Act, 21 U.S.C. § 360i, and 21 CFR § 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 § 803.17. FDA 483 Item 13. Specifically, your firm did not have written medical device reporting procedures for receiving, evaluating, and submitting MDR reports to the FDA.
Your firm is advised to search its archived records and contact and consult the Office of Device Evaluation of CDRH in order to determine whether your firm's water purification tanks using the current resin and carbon materials are in fact exempt from the 510(k) premarket notification requirements. As per 21 CFR § 876.5665, water purification tanks distributed for hemodialysis use are classified as a Class II device requiring submission of a 510(k) application to the FDA for review and clearance prior to their commercial distribution in the United States.
The inspection documented that the GE Infrastructure, Water & Process Technologies acquired the Ionics Ahlfinger Water Company and changed its name to GE Ionics in 2005. This information was also posted in past news releases on the internet.
We are concerned that GE Ionics may not have adequately maintained its records to prove that its current water purification tanks are in fact exempt from the 510(k) premarket notification requirements. Your firm's on-site manager provided the investigator with an unsigned and brief memo, dated October 16, 1997, stating that water purification tanks were considered "preamendment" devices as they have been delivered and installed prior to May 28, 1976, and therefore, exempt from the Agency's premarket notification requirements. The information documented in this memo was based on verbal and limited information provided by a former employee without providing any substantial supporting documentation to validate its material facts.
You must provide CDRH and this office a substantial explanation and historical records including sales invoices, product labels/labeling, product brochures, material specifications, and other relevant documents that attested that the Ionics Ahlfinger Water Company had actually marketed, distributed, and installed the same water purification tanks for hemodialysis use before May 28, 1976. To ensure compliance with 21 CFR § 807.81(a)(3), 820.40, 820.70(b), 820.181, and 820.30(i), your firm is directed to conduct and document a comprehensive review and comparison of the material specifications and manufacturing processes of the water purification tanks that have been distributed and installed for hemodialysis use since and before May 28, 1976 in order to assess if any significant changes in the device's designs, materials, chemical compositions, and manufacturing processes have occurred after May 28, 1976, and therefore, could affect the device's safety or effectiveness that may warrant a 510(k) submission. Warning Letter Item 1 cited your firm for not evaluating and documenting a past design change. Your firm's assessment of past design changes is to be included in your 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 CFR 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 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.
Todd W. Cato
Acting Dallas District Director
Mr. Dale Wray, Director, Plant Operations
GE Infrastructure, Water & Process Technologies
Number 2 Arrowhead Industrial Blvd.
Saint Peters, Missouri 63376-1021
Mr. Edward Joseph Berges, Plant Manager
GE Ionics, Inc.
4740 Bronze Way
Dallas, Texas 75236-1999