September 19, 2012

 

 

 

Gabor J. Racz, Jr., President

Epimed International, Inc.

7445 Las Colinas Boulevard

Irving, Texas 75063

 

Dear Mr. Racz:

During an inspection of your firm located in Johnstown, New York,on May 1 through May 17, 2012, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures various models of R-F Thermocouple Electrode and R-F Cannula.  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 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 requirements of the Quality System regulation found at Title 21, Code of Federal Regulations (CFR), Part 820.

 

We received a response from Mr. Preston Frasier dated June 7, 2012, concerning our investigator’s observations noted on the Form FDA 483 (FDA 483), List of Inspectional Observations, which was issued to your firm. For all corrections, your firm provided a target completion date of November 30, 2012. The adequacy of your firm’s response to FDA 483 Observations 2 through 11 cannot be determined at this time because your firm did not provide documentation to support implementation of corrective actions and preventative actions. 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 procedures for acceptance of incoming product to ensure that product conforms to specified requirements, as required by 21 CFR 820.80(b). For example:

 

a.   Your firm conducts acceptance testing on the R-F Thermocouple Electrodes (R-F Probes) without knowledge of the device’s original manufacturing specifications from the initial manufacturer, or how changes made to the device while at the firm, including sterilization cycles, will affect the device.

 

The adequacy of your firm’s response dated June 7, 2012, cannot be determined at this time. Although your firm has opened CAPA # (b)(4) to address this observation and stated that it will revise the Quality System manual sections associated with design control and purchasing to address the observation, no evidence of procedures or systemic implementation is provided. 

 

b.   Your firm failed to follow its own procedures for testing of product, SOP-484, RF Probe Assembly Inspection, Revisions 0-1, requiring Ohms testing, but accepted (b)(4) lots (from our review of (b)(4) records of R-F Probe Assembly Inspections) into inventory. Further, your firm accepted lots of devices that failed testing, and did not have documentation of actions taken as required by the Material Review Board procedure, QAP-1301, Control of Nonconforming Products, Rev. 13.

 

The adequacy of your firm’s response dated June 7, 2012, cannot be determined at this time. Your firm opened CAPA #(b)(4) to address the nonconformances in the incoming inspection activities, and determined that it will have to evaluate inspection records associated with R-F probes currently in inventory. Additionally, your firm determined that staff will have to be retrained on nonconforming product procedures.  No procedures or evidence of implementation was provided.  

 

2.   Failure to establish and maintain procedures for receiving, reviewing, and evaluating complaints by a formally designated unit, as required by 21 CFR 820.198(a). For example, our review of (b)(4) of (b)(4) complaints related to failures of the R-F Thermocouple Electrodes revealed the following:

 

a.   When your firm’s complaint investigation concludes that the R-F probe malfunctioned, the original specification developer/supplier of the R-F probe is not routinely contacted to determine the cause and determine appropriate corrective action, as required by your firm’s complaint handling procedure, QAP-2201, Complaint Handling, Rev. 16, Section 5.4.2.

 

The adequacy of your firm’s response dated June 7, 2012, cannot be determined at this time. Although your firm opened CAPA #(b)(4) to address the inconsistencies in complaint investigations and it is planning to review the procedure used to conduct complaint investigations, no revised procedures or evidence of implementation were provided.

 

b.   The complaint files reviewed make statements of “extensive investigation” that determine a root cause; however, no documentation was provided to support the extensive investigation or the conclusions. Your examination of probe batch history records to demonstrate that the devices met established acceptance criteria when distributed, as required by SOP QAP-2201, Complaint Handling, Rev. 16, Section 5.7, was not always conducted.

 

The adequacy of your firm’s response dated June 7, 2012, cannot be determined at this time. Although your firm opened CAPA #(b)(4) to address the inconsistencies in complaint investigations and it is planning to review the procedure used to conduct complaint investigations, no revised procedures or evidence of implementation were provided. 

 

c.   Documented failure investigations on returned nonconforming devices to identify product failure were carried out using different test methods from the established acceptance criteria identified in SOP 484, R-F Probe Assembly Inspection.

 

The adequacy of your firm’s response dated June 7, 2012, cannot be determined at this time. Although your firm opened CAPA #(b)(4) to address the inconsistencies in complaint investigations and it is planning to review the procedure used to conduct complaint investigations, no revised procedures or evidence of implementation were provided. 

 

3.   Failure to establish and maintain procedures to ensure that all purchased or otherwise received product and services conform to specified requirements, as required by 21 CFR 820.50. For example, your firm does not have an agreement with its supplier, (b)(4), which defines responsibility for device attributes and quality requirements. Specifications for the device are  not defined between (b)(4) and Epimed. Further, although (b)(4) is listed on your firm’s Approved Supplier List, IHR-603, Revision 4, as a critical supplier, your firm failed to follow its own procedure in requiring critical suppliers to have a Change Notification Contract. Your firm’s procedure, QAP-601, Rev. 18, Supplier Assessment, requires a file for each supplier that includes product specifications and supplier assessments; however, upon request, no supplier file for (b)(4) was provided to the investigator.

 

The adequacy of your firm’s response dated June 7, 2012, cannot be determined at this time. Although your firm opened CAPAs #(b)(4), #(b)(4), and #(b)(4) to obtain documentation from the original specification developer, (b)(4), and to address changes to the complaint handling, design, and supplier control procedures, no revised procedures or evidence of implementation were provided.  

 

4.   Failure to establish and maintain procedures to control the design of the device in order to ensure that specified design requirements are met, as required by 21 CFR 820.30(a). For example:

 

a.   Your firm has not specified design validation requirements for the R-F Cannula to ensure the device conforms to defined user needs and intended uses. There was no information to identify the lots used for validation activities, nor evidence supporting the conclusions based on the test methods used.      

 

The adequacy of your firm’s response dated June 7, 2012, cannot be determined at this time. Although your firm opened CAPA #(b)(4) to address the observation, and stated that your firm will review Design Validation Protocol #170, Revision 1, to amend, address, and clarify items noted in the observation, no revised procedures or evidence of systemic implementation were provided. Your firm noted that parts of the Quality Management System will be revised to prevent future occurrences. 

 

b.   The batch history record documenting the manufacture of (b)(4) R-F Introduction Cannulas, Epimed Lot #020304, used for design verification activities, is not complete.  Units that did not meet acceptance criteria for Dielectric Withstand were not accounted for, and no documentation of why design verification activity is acceptable with rejected units was provided.  Additional failing units that were tested for design verification and noted in the Dielectric Withstand testing raw data were not accounted for in the Summary Report.

 

The adequacy of your firm’s response dated June 7, 2012, cannot be determined at this time. Although your firm has opened CAPA #(b)(4) to address the observation and stated that your firm will review and amend the Design Verification Protocol #153 to amend, address, and clarify items noted in the observation, no revised procedures or systemic evidence of implementation were provided. Your firm noted that parts of the Quality Management System will be revised to prevent future occurrences. 

 

c.   Not all design changes were adequately verified or validated before implementation after changes were made and design change procedure, QAP-901, Process and Product Change Control, Revision 4, was not followed.

 

The adequacy of your firm’s response dated June 7, 2012, cannot be determined at this time. Although your firm has opened CAPA #(b)(4) to address the observation and has stated that your firm will amend, address, and clarify items noted in the observation, no revised procedures or systemic evidence of implementation were provided. Your firm noted that it will revise parts of the Quality Management System to prevent future occurrences. 

 

d.   The protocol used for design transfer activities (“Validation Protocol #151 Master Plan RF Introduction Cannula,” Revision 1, dated 09/09/2004) required (b)(4) consecutive production runs to be completed.  However, there is no documentation of the production runs being carried out. In addition, the raw data demonstrating that acceptance criteria were met, as well as the device specifications properly transferred to production, were not available.

 

The adequacy of your firm’s response dated June 7, 2012, cannot be determined at this time. Although your firm has opened CAPA #(b)(4) to address the observation and noted that your firm will review and amend the Validation Protocol #152 to amend, address, and clarify items noted in the observation, no revised procedures or systemic evidence of implementation were provided. Your firm noted that it will revise parts of the Quality Management System to prevent future occurrences.

 

e.   Your firm failed to identify all inputs critical to ensuring the intended use of the RF Cannula by not considering the interface requirements of the R-F Cannulas with the RF probes and RF generators with which they may be used as inputs.

 

The adequacy of your firm’s response dated June 7, 2012, cannot be determined at this time. Although your firm opened CAPA #(b)(4) to address the observation and noted that it will review and amend procedures to amend, address, and clarify items noted in the observation, no revised procedures or systemic evidence of implementation were provided. Your firm noted that it will revise parts of the Quality Management System to prevent future occurrences. 

 

f.    Your firm failed to document all outputs critical to ensuring the intended use of the R-F Cannula. Specifications were not developed, acceptance criteria were not developed to ensure proper functioning of the RF Cannula with the RF probes and RF generators, and the source of design output specifications was not documented.

 

The adequacy of your firm’s response dated June 7, 2012, cannot be determined at this time. Although your firm opened CAPA #(b)(4) to address the observation and noted that your firm will review and amend procedures to amend, address, and clarify items noted in the observation, no revised procedures or systemic evidence of implementation were provided.   Your firm noted that it will revise parts of the Quality Management System to prevent future occurrences.

 

Our inspection also revealed that all models of the R-F Thermocouple Electrode are adulterated under section 501(f)(1)(B) of the Act, 21 U.S.C. § 351(f)(1)(B), because your firm does 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 under section 520(g) of the Act, 21 U.S.C. § 360j(g).  For a device requiring premarket approval, the notification required by section 510(k) is deemed satisfied when a PMA is pending before the agency.  [21 CFR 807.81(b)]  The kind of information that your firm needs to submit in order to obtain approval or clearance for the device is described on the Internet at http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/default.htm. The FDA will evaluate the information that your firm submits and decide whether the product may be legally marketed.

 

We acknowledge that your firm submitted a 510(k) for the R-F Thermocouple Electrode including nitinol probes on August 26, 2010.  However, that 510(k) was found Not Substantially Equivalent on September 1, 2011.  Your firm’s response to FDA 483 Observation 1 is inadequate. While we acknowledge that your firm submitted a premarket notification to the FDA on June 6, 2012, your R-F Thermocouple Electrode has not yet been cleared for marketing. Additionally, your firm’s response fails to address the safety and efficacy of the devices that are currently on the market. 

 

A follow-up inspection will be required to assure that corrections and/or corrective actions are adequate. 

Your firm should take prompt action to correct the violations addressed in this letter. Please be advised that our September 1, 2011, letter to your firm indicated that any commercial distribution of the device subject of 510(k) K102434 prior to the approval of a PMA would be a violation of the Act.  We request that your firm immediately cease the commercial distribution of the R-F Thermocouple Electrodes.  Continued distribution of violative devices and/or failure to promptly correct the violations detailed in this letter may result in regulatory action being initiated by the FDA without further notice.  These actions include, but are not limited to, seizure, injunction, and civil money penalties.  Also, federal agencies may be advised of the issuance of 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 violations 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 business days from the date you receive this letter of the specific steps your firm has taken to correct the noted violations, as well as an explanation of how your firm plans to prevent these violations, or similar violations, from occurring again.  Include documentation of the corrections and/or corrective actions (including any systemic corrective actions) that your firm has taken.  If your firm’s planned corrections and/or corrective actions will occur over time, please include a timetable for implementation of those activities.  If corrections and/or corrective actions cannot be completed within fifteen business days, state the reason for the delay and the time within which these activities will be completed. Your firm’s response should be comprehensive and address all violations included in this Warning Letter.

 

Your written response should be sent to Dean R. Rugnetta, Compliance Officer, U.S. Food and Drug Administration, 622 Main St., Suite 100, Buffalo, NY 14202. Refer to NYK-2012-24 when replying. If you have any questions about this letter, please contact Compliance Officer Dean R. Rugnetta at (716) 846-6207 or E-mail at dean.rugnetta@fda.hhs.gov.

 

Finally, you should know that this letter is not intended to be an all-inclusive list of the violations at your firm’s facility.  It is your firm’s responsibility to ensure compliance with applicable laws and regulations administered by FDA.  The specific violations noted in this letter and in the Inspectional Observations, FDA 483, issued at the close of the inspection may be symptomatic of serious problems in your firm’s manufacturing and quality management systems.  Your firm should investigate and determine the causes of the violations, and take prompt actions to correct the violations and bring the products into compliance. 

                                                                                

/S/                                                           

                                                                                                                                                      

 

cc:       

 

Vice President of Manufacturing Operations