| Public Health Service Food and Drug Administration |
San Francisco District |
Department of Health and Human Services
WARNING LETTER
VIA UPS EXPRESS
December 22, 2010
Benjamin Krempel
Chief Executive Officer
Aqueduct Medical, Inc.
665 Third Street, Suite 20
San Francisco, CA 94107
Dear Mr. Krempel:
During an inspection of your firm located in San Francisco, California on April 22, 2010, through May 17, 2010, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures the AqueCool™ Rapid Recovery System, AqueVest™ device, and the AqueCool™ Masque device. Under section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. 321(b), 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 function of the body.
Our inspection revealed that the AqueCool™ Rapid Recovery System, AqueVest™ device and AqueCool™ Masque devices are 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). Specifically, you are marketing the device with claims of rapid recovery and/or accelerated healing, which exceeds the limitations of 21 CFR 890.9 for devices classified under 21 CFR 890.5720 as Water circulating hot or cold packs. 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 C.F.R. 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 http://www.fda.gov/cdrh/devadvice/3122.html. The FDA will evaluate the information you submit and decide whether your product may be legally marketed.
This inspection also 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. We received a response from you dated September 13, 2010, concerning our investigator's observations noted on the Form FDA 483, List of Inspectional Observations that was issued to you. We address this response below, in relation to each of the noted violations. These violations include, but are not limited to, the following:
1. Failure to establish and maintain adequate procedures to ensure that where the results of a process cannot be fully verified by subsequent inspection and test, the process shall be validated with a high degree of assurance and approved according to established procedures, as required by 21 CFR 820.75(a). Specifically, there is no process validation study for the radio frequency welding process that is used to weld flanges onto the bladder that is a component of the AqueCool masques and AqueVests.
We reviewed your response and conclude that it is inadequate because you have not provided any evidence of a corrective action or systemic corrective action. You provided your product specifications list for the face mask with a list of quality control tests you use. You also included a letter from (b)(4) that indicates no formal validation is required because you use 100% static inflation testing and visual inspection. It is unclear what this testing entails and how it absolves your firm from completing the required process validation for a welding process.
2. Failure to establish and maintain adequate procedures for receiving, reviewing, and evaluating complaints by a formally designated unit, as required by 21 CFR 820.198(a). For example:
a. Complaint Investigation Reports (CIR) for Customer Service Reports (CSR) # (b)(4) do not include investigations into the cause of non-conformities related to leaking vests and masques.
b. There were two different Customer Service Reports (CSR) with the number (b)(4) and two different CSRs with the number (b)(4). These reports represented different complaints but were given duplicate CSR numbers.
c. Twenty-eight of twenty-eight Customer Service Reports were not adequately completed to include: name of the device, date the complaint was received, or customer address and phone number.
We reviewed your response and conclude that it is inadequate because you have not provided evidence of a corrective action or a systemic corrective action. You provided training records for two employees, although it is not clear which procedures these documents cover. You also provided a blank "CSR Log Sheet" and a "Weekly Status Report" dated July 26 - July 30, 2010. It is not clear how these documents address the above deficiency.
3. Failure to ensure that any complaint involving the possible failure of a device, labeling, or packaging to meet any of its specifications shall be reviewed, evaluated, and investigated, unless such investigation has already been performed for a similar complaint and another investigation is not necessary, as required by 21 CFR 820.198(c). For example:
a. The documents: "Quality Records Policy/Procedure," (b)(4)."Customer Service Report," (b)(4) (CSR);and "Customer Investigation Report-CIR," (b)(4) serve as the complaint handling procedure and lack instructions or guidance on how to review, evaluate, and investigate any complaint involving the possible failure of a device, labeling, or packaging to meet any of its specifications.
b. CSR#(b)(4)outlined a complaint that reported a ''patient had a very bad reaction to the product." There was no investigation. The CSR indicates that the action or investigation required was a ''refund.''
c. No investigation was conducted for the following complaints that reported leaking masques: CSR#(b)(4)(no date), (b)(4)
d. No investigation was conducted for the following complaints that reported missing device components: CSR#(b)(4)
We reviewed your response and conclude that it is inadequate because you have not provided evidence of a corrective action or systemic corrective action. You provided training records for two employees, a blank "CSR Log Sheet," and a "Weekly Status Report," dated July 26 - July 30, 2010. You also provided Engineering Change Order Form No.(b)(4) The specific change is not outlined on this form.
4. Failure to ensure that any complaint that represents an event which must be reported to FDA under part 803 of this chapter shall be promptly reviewed, evaluated, and investigated by a designated individual(s) and shall be maintained in a separate portion of the complaint files or otherwise clearly identified, as required by 21 CFR 820. 198(d). For example:
a. Customer Service Report#(b)(4) reported a leaking AqueCool Masque, but the leaking masque was not identified as a device failure per the answer to the first question in the Post-Service Questionnaire on the Customer Service Report.
b. Customer Service Report#(b)(4) reported the, ''patient had a very bad reaction to the product," but problem was not identified as a device failure, nor was it identified as an "MDD adverse event, Vigilance reporting event," on the Post-Service Questionnaire section of the Customer Service Report.
We reviewed your response and conclude that it is inadequate because you have not provided evidence of a corrective action or systemic corrective action. You provided training records for two employees, a blank "CSR Log Sheet," and a "Weekly Status Report," dated July 26 - July 30, 2010. You also provided Engineering Change Order Form No. (b)(4) The specific change is not outlined on this form.
5. Failure to establish and maintain 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). Specifically, according to the Operations Manager, there is no documented instruction for the life test for flow rate and temperature. The life test is performed on newly produced and repaired AqueCool Rapid Recovery Systems to ensure each system meets specified requirements.
We reviewed your response and conclude that it is inadequate because you have not provided evidence of a corrective action or systemic corrective action. You explain that document (b)(4)(AqueCool service manual) was updated to include a life test check for each unit. The flow chart located in (b)(4) is not prescriptive in the tests required for each type of failure.
6. Failure to establish and maintain procedures for changes to a specification, method, process, or procedure, as required by 21 CFR 820.70(b). Such changes shall be verified or where appropriate validated according to 21 CFR 820.75, before implementation and these activities shall be documented. For example:
a. "Production and Process Control Policy / Procedure," (b)(4) states, " ... changes to specifications, equipment, assembly procedures or related manufacturing processes will be reviewed and approved before usage." However, it lacks the requirement of verification or validation of such changes before implementation.
b. The "Production and Process Control Policy / Procedure" was not implemented when the continuity test was discontinued for the AqueCool Rapid Recovery System. This change was not reviewed and approved prior to implementation.
c. The "Production and Process Control Policy / Procedure" was not implemented when the (b)(4) thermocouple temperature recorder, digital multimeter, and flow rate meter were replaced by the AqueCool Service Tool. This change was not reviewed and approved prior to implementation.
We reviewed your response and conclude that it is inadequate because you have not provided evidence of a corrective action or systemic corrective action. The document you provided, (b)(4) is the AqueCool service manual, and not a manufacturing process procedure. This document does not appear to include procedures for changes to a specification, method, process, or procedure, as required by 21 CFR 820.70(b). It also does not appear to include validation or verification of the AqueCool Service Tool. You explain that verification is completed by showing consistency between the original test set-up and AqueCool Service Tool, but this is not adequate to address the requirements of this part.
7. Failure to establish and maintain adequate procedures to ensure that all inspection, measuring, and test equipment, including mechanical, automated, or electronic inspection and test equipment, is suitable for its intended purpose and is capable of producing valid results, as required by 21 CFR 820.72(a). For example, the "Production and Process Control Policy / Procedure", (b)(4) states test equipment is to be inspected on a (b)(4) basis for maintenance and calibration. The calibration equipment inspection was conducted (b)(4) only from January 8, 2007, to October 4, 2007. The last calibration equipment inspection was conducted on April 2, 2008. The AqueCool Service Tool required a calibration on October 26, 2008, and was used until April 22, 2010, despite requiring calibration.
We reviewed your response and conclude that it is inadequate because you have not provided evidence of a corrective action or systemic corrective action. You explain that all equipment requiring calibration has been brought up to date and you provided the calibration certificates along with a calibration log that is reviewed at the monthly manager meeting. You did not provide a procedure or evidence of any corrective actions.
8. Failure to establish and maintain adequate procedures to control all documents, as required by 21 CFR 820.40. For example, the "Document and Data Control Policy / Procedure," (b)(4) states documents released to the electronic vault are password protected as a read-only document to prevent unwanted or uncontrolled changes and the physical document vault is locked. However, the electronic vault is not currently password protected nor is the physical document vault locked.
We reviewed your response and conclude that it is inadequate because you have not provided evidence of a corrective action, or systemic corrective action. You indicate that controlled documents are now stored in a locked cabinet where the Operations Manager holds the only key. In addition, the electronic vault users have unique user names and passwords to track who makes changes to controlled documents. There was no procedure or other evidence provided to support these changes were made.
9. Failure to retain all records required by this part for a period of time equivalent to the design and expected life of the device, but in no case less than two years from the date of release for commercial distribution by the manufacturer, as required by 21 CFR 820.180(b). Specifically, the Device History Records for the AqueCool Rapid Recovery Systems serial number (b)(4) and serial number (b)(4) could not be located.
We reviewed your response and conclude that it is inadequate because you have not provided evidence of a corrective action or a systemic corrective action. You indicate that you created replacement Device History Files for #(b)(4) and #(b)(4) however it is unclear what you have done to prevent this type of problem from recurring.
10. Failure to establish and maintain adequate procedures for identifying training needs and ensuring that all personnel are trained to adequately perform their assigned responsibilities and to ensure the training shall be documented, as required by 21 CFR 820.25(b). Specifically, the Operations Manager is responsible for document control, purchasing/supplier evaluation, control of monitoring and measuring devices, disposition of non-conforming products, and work environment control, yet the Operations Manager has not been trained to the respective policies/procedures.
We reviewed your response and conclude that it is inadequate because you have not provided evidence of a corrective action or systemic corrective action. You provided training records for two employees indicating retraining on several procedures. It is not clear what revision of each of the procedures was part of the training, or what the procedures include.
11. 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 to ensure that the quality system satisfies the requirements of this part and the manufacturer's established quality policy and objectives, as required by 21 CFR 820.20(c). For example, the last management review was conducted on August 6, 2007. The meeting agenda for the August 6, 2007, meeting has the next meeting scheduled for February 25, 2008. There is no evidence that this February meeting occurred or that any subsequent meeting occurred. According to the Chief Executive Officer, there is currently no schedule for management reviews.
We reviewed your response and conclude that it is inadequate because you have not provided evidence of a corrective action or systemic corrective action. You provided, "Management Review Policy/Procedure," (b)(4) The revision date of this procedure dates back to 2004, so it is unclear how providing this procedure for review addresses the above deficiency since it does not appear the procedure was being followed at the time of inspection. You also provided "Internal Audits Policy/Procedure," (b)(4) which appears to be an audit record. This record states that an audit was conducted from July 7, 2010, through July 12, 2010, and that all procedures were audited except design and development. The procedure/record does not appear to correspond directly to all the procedures within the scope of the audit. There is no procedure dictating how the audit is to be conducted.
12. 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. These quality audits shall be conducted by individuals who do not have direct responsibility for the matters being audited, as required by 21 CFR 820.22. For example, the "Aqueduct Medical Responsibility Assignments" document, updated April 20, 2010, indicates the Chief Executive Officer has the responsibility of conducting quality audits. The Chief Executive Officer also has direct responsibility over the matters being audited such as design and development, control of non-conforming product, corrective and preventive action, infrastructure management, and work environment control.
We reviewed your response and conclude that it is inadequate because you have not provided evidence of a corrective action or systemic corrective action. You provided an organizational chart and a list of responsibilities as they pertain to the CEO, Engineering, and the Operations Manager. It is indicated that the CEO has responsibility for conducting quality audits. It appears the CEO also has direct responsibility over design and development and work environment control. The quality audits are to be completed by those who do not have direct responsibility over the matters being audited.
Our inspection also revealed that your AqueCool Rapid Recovery System and associated masks and vests used as accessories with the system 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 device that is required by or under section 519 of the Act, 21 U.S.C. 360i, and 21 C.FR Part 803 - Medical Device Reporting (MDR) regulation.
Significant deviations include, but are not limited to, the following:
1. Failure to develop, implement, and maintain complete MDR procedures for the documentation and record keeping requirements for all medical device reports and information submitted to manufacturers and/or FDA, as required by 21 CFR 803.17(b)(2).
2. Failure to maintain written MDR procedures as evidenced by the use of an out-of-date FDA guidance document for MDR reporting that is part of "Quality Records Policy / Procedure," (b)(4) The out-of-date guidance is part of a table on page 7 of the procedure.
We reviewed your response and conclude that its adequacy cannot be determined because you have not submitted your written MDR procedure (b)(4), that contains the table, "FDA in icedence [sic] Reporting Guideline." Therefore, the adequacy of this procedure cannot be determined.
A follow up inspection will be required to assure that corrections are adequate.
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 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 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: Mr. Russell A. Campbell, Compliance Officer, 1431 Harbor Bay Parkway, Alameda, CA 94052. If you have any questions about the content of this letter please contact: Mr. Campbell at (501)337-6861.
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,
/S/
Barbara J. Cassens
District Director
San Francisco District
U.S. Food and Drug Administration
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