Inspections, Compliance, Enforcement, and Criminal Investigations
Rhytec, Inc. 24-Apr-07
Department of Health and Human Services
| Public Health Service |
Food and Drug Administration
|New England District |
One Montvale Avenue
Stoneham, Massachusetts 02180
FAX: (781) 596-7896
VIA FEDERAL EXPRESS
April 24, 2007
Chief Executive Officer
130 Turner Street
Waltham, Massachusetts 02453-8901
Dear Mr. Goble:
During an inspection of your firm located in Waltham, MA on December 13, 2006 through January 18, 2007, investigators from the United States Food and Drug Administration (FDA) determined that your firm distributes the Portrait Plasma Skin Resurfacing (PSR3) System. Under section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. 321(h), this product is a device because it is intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or intended to affect the structure or 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. We received a response from Robert Zoletti, Director of Regulatory Affairs and Quality Assurance, dated February 9, 2007 concerning our investigators' observations noted on the Form FDA 483, 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 for design validation to include risk analysis, as required by 21 CFR 820.30(g). For example procedures to control the design process of the Portrait PSR3 System are not complete because they are inadequate to complete a risk analysis. Inadequacies in the design control process include:
• Severity levels and likelihood levels are not defined.
• There is no procedure to calculate hazard score.
• Maximum acceptable risk is not defined.
• Failure to follow [redacted] and [redacted] reference standard as claimed
• A maximum tolerable risk has not determined for use in hazard scoring.
• Risk analysis was not evaluated for the hazard of inadequate labeling when risk reduction was made through product labeling for treatment revisions and new protocol development.
• Risk analysis was not performed for a software change that affected the hazards of the device.
We have received your response and have concluded that it is inadequate. You state that you have revised your Quality System procedure to determine maximum tolerable risk, and that your risk management procedure is to be reviewed and replaced based on the outcome of the review. You state that you are revising your procedures to comply with [redacted] and those that work in the risk management process are to receive training on the new procedure by February 28, 2007. No documentation of the procedure changes or training has been received by FDA.
2. Failure to establish and maintain procedures for implementing corrective and preventive actions for analyzing 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 quality procedures do not contain sufficient instructions for the analysis and monitoring of quality data using appropriate statistical methodology to identify potential sources of nonconforming product. Multiple complaints involving serious injury are attributed to user error; however, the complaint information has not been adequately analyzed to identify potential quality problems with the device.
We have received your response and have concluded that it is inadequate. You state that a new Quality Review Procedure has been developed to conduct regular meetings to monitor and analyze quality system metrics and quality plans, such as internal and external audit results, CAPAs, Complaints and Reportable Incidents, and Field Service Reports. Corrective action is to be completed by February 28, 2007. No documentation of the procedure changes has been received by FDA.
3. Failure to establish and maintain procedures for verifying or validating the corrective and preventative action to ensure that such action is effective and does not adversely affect the finished device, as required by 21 CFR 820.100(a)(4). For example the actions generated for two CAPAs were not verified or validated as effective or completed per your CAPA procedure.
We have received your response and have concluded that it is inadequate. You state that you will be reviewing your CAPA procedures. You state your corrective action completion date is March 31, 2007. However, no documentation of changes to your CAPA procedures has been received by FDA.
4. Failure to establish and maintain procedures to review, evaluate, and investigate any complaint involving the possible failure of a device to meet any of its specifications, as required by 21 CFR 820.198(c). For example your firm's complaint and MDR handling procedure is inadequate for the evaluation of complaints to determine if an investigation is needed and to conduct an investigation of a possible device failure. For an MDR which referenced burns and open lesions on patients the physician reported that the device was "running hot." The device was serviced and failed with an electrical error related to energy output. No investigation was made into the failure of the device to meet specification.
We have received your response and have concluded that it is inadequate. You state that you revised your procedures to incorporate the investigation of possible device failure or malfunction, and your corrective action completion date is February 16, 2007. No documentation of the procedure changes has been received by FDA.
5. Failure to establish and maintain procedures for documenting all corrective and preventive activities and their results., as required by 21 CFR 820.100(b). For example, no formal corrective or preventive action was generated for 25 complaints reviewed during this inspection per the CAPA procedure. However, for 10 of these complaints the complaint form indicated that corrective or preventive action had occurred. These actions were not verified or validated.
We have received your response and have concluded that it is inadequate. You state that existing complaints are under review to determine if a CAPA is required. You state that CAPA procedure training has been given and that your complaint handling procedure has been revised to include a determination if a CAPA is required. Also you state that your new Quality Review Procedure includes CAPA's. You state your corrective action completion is expected by March 31, 2007. No documentation of these changes to your CAPA system has been received by FDA.
6. Failure to establish procedures for identifying training needs and ensure that all personnel are trained to adequately perform their assigned responsibilities, and failure to document training, as required by 21 CFR 820.25(b). For example:
• A training procedure has not been developed for sale representatives and contract sales personnel on how to safely and effectively instruct physicians in the use of the device.
• Documentation of training is not consistently maintained.
• Sales force is not trained in complaint handling.
We have received your response and have concluded that it is inadequate. You state that your training records have been improved, and that training sessions have been conducted and documented for new sales staff and refreshed for current staff. You state you are developing a new Sales Training SOP that is to be released March 15, 2007. No documentation of your corrective actions has been received by FDA.
7. Failure to establish and maintain procedures to record any device identifications and control numbers used in the review, evaluation, and investigation of any complaint, as required by 21 CFR 820.198(e)(3). For example your complaint investigations do not consistently contain the serial number of the device related to the complaint or MDR.
We have received your response and have concluded that it is inadequate. You state that your Complaint Handling Procedure has been revised to require that serial numbers be obtained; however, no documentation of your corrective action has been received by FDA.
Our inspection also revealed that your Portrait PSR3 System 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 the device 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:
8. Failure to develop, maintain, and implement written MDR procedures for a standardized review process or procedure for determining when an event meets the criteria for reporting, as required by 21 CFR 803.17(a)(2). For example the Complaint Handling and Vigilance Reporting Procedure is inadequate in that it lacks investigational instructions to acquire information for complete evaluation of whether a complaint meets the criteria for reporting.
We have received your response and have concluded that it is inadequate. You state that existing complaints will be reviewed in accordance with your revised complaint handling procedure, and newly implemented decision tree to evaluate and document the reporting decision. You state that MDR reporting will occur as determined necessary. No documentation of your new procedures has been received by FDA. You state your corrective action is to be completed by March 15, 2007.
9. Failure to report to the FDA within 30 calendar days after the day that the firm received or otherwise became aware of information, from any source, that reasonably suggests that a marketed device may have caused or contributed to a death or serious injury as required by 21 CFR 803.50(a)(1). For example no MDRs were filed for 12 complaints of serious injury that the device may have caused, and four MDRs were submitted in excess of 30 days.
We have received your response and have concluded that it is inadequate. You state that upon receipt of a complaint it cannot always be determined if it is a permanent impairment and medical intervention may not take place immediately. You state that per your labeling there may be temporary skin changes for up to six months after treatment, and that it may be too soon to determine if there is a reportable issue within 30 days after receiving a complaint. We note that a manufacturer of a device must report under Part 803 within 30 days of becoming aware of information that reasonably suggests that the device may have caused or contributed to a death or serious injury. Thus, if the injury may be a reportable event because it may result in permanent impairment, an adverse event report is required. You state that an Agency Report Decision Tree will be used to document the reporting decision for all complaints when entered into your system. No documentation has been received. You state that corrective action is to be completed by March 15, 2007.
10. Failure to provide a statement explaining why information was incomplete and the steps taken to obtain the information, as required by 21 CFR 803.50(b)(3). For example:
• Serial number is missing on four MDRs.
• Age or date of birth missing on five MDRs.
• No name or patient identifier on three MDRs.
• No patient weight on seven MDRs.
We have received your response and have concluded that it is inadequate. You state that patient identifier information is considered protected information and is often difficult to obtain from customers, and that patient weight is not considered a factor in the skin treatment. You state a new complaint handling procedure has been released that requires patient data be requested from the health care provider, and that a database has been created to obtain the serial number when devices are shipped. No documentation has been received. You state that corrective action is to be completed by February 28, 2007.
Our inspection also revealed that your Portrait PSR3 System 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 the device that is required by or under section 519 of the Act, 21 U.S.C. 360i, and 21 C.F.R. Part 806 - Reports of Corrections and Removals regulation. Specifically, a correction and removal, conducted to reduce a risk to health posed by a device, was not reported in writing to the FDA. Significant deviations include, but are not limited to, the following:
11. Failure to have justification for not reporting a correction and removal action to the FDA that included conclusions, follow-ups, and reviews by a designated person in the records, as required by 21 CFR 806.20(b)(4) and 21 CFR 806(a). For example the justification for not reporting a correction which reduced a risk to public health was not maintained in the file for a software upgrade in September 2006 which controls the energy output of the device. The FDA evaluated this correction and removal action and classified it as a Class II recall (Z-0397-2007).
We have received your response and have concluded that it is inadequate. You state that your procedures did not require documentation for remedial action decisions. You state that you are revising your procedures to require justifications for not reporting a correction and removal action to be documented. No documentation of your corrective action has been received by FDA.
Our inspection also revealed that in September, 2006, you modified the software of the Portrait PSR3 System to affect the power level output of the device. This modification constitutes a significant change or modification that could significantly affect the safety or effectiveness of the device. Therefore, the Portrait PSR3 System 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(0) the Act, 21 U.S.C. 352(o), because you did not notify the agency of your intent to introduce the modified 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. 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.aov/cdrh/devadvice/3122.html. The FDA will evaluate the information you submit and decide whether your product may be legally marketed.
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: Anthony Costello, Compliance Officer. If you have any questions about the content of this letter please contact Mr. Costello at 781-596-7716 or fax at 781-596-7896.
Finally, you should know that this letter is not intended to be an all-inclusive list of the violation(s) at your facility. It is your responsibility to ensure compliance with applicable laws and regulations administered by FDAs. The specific violation(s) 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 violation(s), and take prompt actions to correct the violation(s) and to bring your products into compliance.
Gail T. Costello
New England District