Inspections, Compliance, Enforcement, and Criminal Investigations

Vygon Gmbh & Co. KG 8/4/14

  

Department of Health and Human Services logoDepartment of Health and Human Services

Public Health Service
Food and Drug Administration
 10903 New Hampshire Avenue
Silver Spring, MD 20993 

 

WARNING LETTER
AUG 4, 2014
 
 
VIA UNITED PARCEL SERVICE
 
Dr. Raymund Heiliger
Chief Executive Officer
Vygon GmbH & Co. KG
100 Prager Ring
Aachen 52070
Germany
 
Dear Dr. Heiliger:
 
During an inspection of your firm located in Aachen, Germany, on March 17, 2014, through March 20, 2014, investigators from the United States Food and Drug Administration (FDA) determined that your firm manufactures intravascular catheters. 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 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 your response, dated April 9, 2014, concerning our investigator’s observations noted on the Form FDA 483 (FDA 483), List of Inspectional Observations, which was issued to your firm.  We address this response below, in relation to each of the noted violations.  Your firm's response dated June 18, 2014, was not reviewed because it was not received within fifteen business days of issuance of the FDA 483. This response will be evaluated along with any other written material provided in response to the violations cited in this Warning Letter. These violations include, but are not limited to, the following:
 
1.    Failure to maintain complaint files and 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, your firm’s complaint handling procedure, Treatment of Customer Complaints (b)(4), does not include requirements to ensure that: 
 
a.    complaints are processed in a uniform and timely manner;
 
b.    oral complaints are documented upon receipt; and
 
c.    complaints are evaluated for medical device reporting (MDR) reportability. 
 
Of the nine complaint files reviewed, none of the complaint files included documentation of your firm's review for MDR reportability or the dates of the investigations. Seven of the files had inaccurate dates as to when the complaint was received. One file indicated information from the investigation was received by telephone; however, no information was documented in the file.   
 
The adequacy of your firm’s response cannot be determined at this time. Your firm stated that it performed a retrospective review of complaints reported on five years of data for MDR reportability. Your firm has reviewed and revised its procedure, Treatment of Customer Complaints (b)(4), to be compliant with Quality System complaint handling requirements. Employees that handle customer complaints will be trained on MDR procedures. However, in your firm’s April 9, 2014, response, your firm did not provide evidence of completion of these corrective actions or evidence of implementation of the new procedures.
 
2.    Failure to establish and maintain procedures for implementing corrective and preventive action, as required by 21 CFR 820.100(a). 
 
For example, Chapter 12 of your firm’s (b)(4) 10, Revision 22, September 17, 2013, lists corrective actions to take when faults or defects are detected during the production process. However, your firm does not appear to have any CAPA procedures that met the requirements of 21 CFR 820.100(a).
 
The adequacy of your firm’s response cannot be determined at this time. Your firm stated that, while it had individual procedures that established corrective actions according to each procedure, it had no CAPA procedure that met the Quality System requirements of 21 CFR 820.100. Your firm committed to developing a CAPA procedure that conforms to the requirements of 21 CFR 820.100(a). However, no CAPA procedure has been provided by your firm for our review.
 
3.    Failure to establish and maintain procedures for verifying the device design to confirm that the design output meets the design input requirements, as required by 21 CFR 820.30(f). 
 
For example, design verification testing conducted for (b)(4) revealed that not all required data were contained or referenced in the Design History File (DHF), such as the identification of the design, the sterilization data, and any test protocols with acceptance criteria approved prior to the start of testing.
 
The adequacy of your firm’s response cannot be determined at this time. Your firm stated that it had included the missing documents in the DHF for (b)(4) and that it will review and revise the procedure, (b)(4), to be compliant with design verification requirements. However, in your firm’s April 9, 2014, response, your firm did not provide evidence of completion of these corrective actions or evidence of implementation of the new procedures.
 
4.    Failure to establish and maintain procedures that define the responsibility for review and the authority for the disposition of nonconforming product, as required by 21 CFR 820.90(b)(1).
 
For example, your firm's nonconforming product procedure, Treatment of Faulty Units (b)(4), Revision 3, dated November 14, 2005, does not include requirements that adequately set forth the review and disposition process and ensure that the disposition of nonconforming product is documented. At least two (b)(4) Forms reviewed for nonconformances did not document the disposition of the nonconforming products. Another (b)(4) Form involved scrapping some units and returning them to the vendor; however, disposition of these units was not documented.
 
The adequacy of your firm’s response cannot be determined at this time. Your firm stated that its procedure, Treatment of Faulty Units (b)(4), will be reviewed and revised to comply with nonconforming product requirements. However, in your firm’s April 9, 2014 response, your firm did not provide evidence of implementation of the revised procedure.   
 
5.    Failure to define the type and extent of control to be exercised over the product, services, suppliers, contractors, and consultants, based on the evaluation results, as required by 21 CFR 820.50(a)(2). For example:
 
a.    Your firm's purchasing control procedure, Supplier Quality Capability (b)(4), Revision 9, dated April 6, 2011, outlines when an initial supplier audit is to be conducted, but does not include requirements outlining the frequency for supplier audits and the criteria for when a supplier audit is to be planned and how it is to be conducted. 
 
b.    Your firm's quality audit procedure, Audit Programm (b)(4), Section 2 – Scope, includes supplier audits as applicable to the procedure; however, it does not include requirements for the frequency of supplier audits, the criteria used for planning when supplier audits will be conducted, or how a supplier audit will be conducted.
 
The adequacy of your firm’s response cannot be determined at this time. Your firm stated that its procedures, Supplier Quality Capability (b)(4) and Audit Programm (b)(4), will be reviewed and revised to comply with purchasing controls requirements. However, in your firm’s April 9, 2014, response, your firm did not provide evidence of implementation of the revised procedures.
 
6.    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, quality audits were not performed at defined yearly intervals per your firm’s quality audit procedure, Audit Programm (b)(4). Seven out of 18 audits for 2013 were not conducted within the yearly frequency requirement per Annex I, Audit frequency. The audit procedure does not include requirements that ensure that re-audits will be conducted when necessary.   
 
The adequacy of your firm’s response cannot be determined at this time. Your firm stated that its procedure, Audit Programm (b)(4), will be reviewed and revised to comply with quality audits requirements. However, in your firm’s April 9, 2014, response, your firm did not provide evidence of implementation of the revised procedure. 
 
Our inspection also revealed that your firm’s 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 CFR Part 803 - Medical Device Reporting. Significant deviations include, but are not limited to, the following:
 
7.    Failure to develop, maintain, and implement written MDR procedures, as required by 21 CFR 803.17. 
 
For example, we reviewed your firm’s procedure, Treatment of Customer Complaints (b)(4), Revision 16, dated September 30, 2013. As written under the Scope, the procedure is intended to describe your firm’s process for complaint handling and vigilance reporting. We determined that the procedure is not an MDR procedure, as required by 21 CFR 803.17.
 
8.    Failure of your firm to submit an event report to FDA no later than 30 calendar days after the day that your firm received or otherwise became aware of information, from any source, that reasonably suggests that a device that your firm markets may have caused or contributed to a death or serious injury, as required by 21 CFR 803.50(a)(1).
 
For example, Complaint #8353 includes information that reasonably suggests that your firm’s device may have caused or contributed to the patient’s death. The Complaint was received by your firm on September 28, 2012.  An MDR was only recently submitted to FDA for the referenced complaint. 
 
9.    Failure of your firm to report to FDA no later than 30 calendar days after the day that your firm received or otherwise became aware of information, from any source, that reasonably suggests that a device that it markets has malfunctioned and that this device or a similar device that your firm markets would be likely to cause or contribute to a death or serious injury if the malfunction were to recur, as required by 21 CFR 803.50(a)(2). 
 
For example, Complaint #7795 includes information that reasonably suggests that the device malfunctioned. The Preamble, in the Medical Devices; Medical UserFacilityandManufacturer Reporting, Certification and Registration; Final Rule, 60 Fed. Reg. 63585 (Dec.
11, 1995), states that a malfunction of a long-term implant is reportable to FDA. There is no information included for the complaint that reasonably suggests that the malfunction of the device would not be likely to cause or contribute to a death or serious injury if it were to recur. Your firm became aware of the event on 06/06/2011 and FDA received an MDR on 07/25/2011.
 
10.    Failure of your firm to establish and maintain MDR event files as required by 21 CFR 803.18(b)(ii).  
 
For example, your firm did not have on file copies of all MDR forms and other information related to the event for complaint #7795.
 
11.    Failure of your firm to submit a supplemental or follow up report to FDA within one month of the day that your firm received information that was not provided because it was not known or was not available when your firm submitted the initial report, as required by 21 CFR 803.56.  
 
For example, FDA has not yet received the supplemental MDRs associated with Complaint #7795 that documents the results of your firm’s 09/05/2011 investigation.
 
We reviewed your firm’s response, dated April 9, 2014, and conclude that it is not adequate. Your firm noted that it will revise the procedure titled, “(b)(4) Treatment of Customer Complaints, Revision 16,” dated 09/30/2013, to include a checklist for reportability of events. The procedure identified as “(b)(4) Treatment of Customer Complaints, Revision 16,” dated 09/30/2013, is not an MDR procedure.  Your firm should develop, maintain, and implement written MDR procedures, as required by 21 CFR 803.17.
 
The eMDR Final Rule requiring manufacturers and importers to submit electronic Medical Device Reports (eMDRs) to FDA was published on February 13, 2014.  The requirements of this final rule will take effect on August 14, 2015. If your firm is not currently submitting reports electronically, we encourage you to visit the following web link for additional information about the electronic reporting requirements:
 
 
If your firm wishes to discuss MDR reportability criteria or to schedule further communications, it may contact the Reportability Review Team by email at
 
U.S. 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 deviations are reasonably related will not be approved until the violations 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, including 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 (which must address systemic problems) 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 thirty business days, state the reason for the delay and the time within which these activities will be completed. Please provide a translation of documentation not in English to facilitate our review. We will notify you regarding the adequacy of your firm’s response and the need to re-inspect your firm’s facility to verify that the appropriate corrections and/or corrective actions have been made.
 
Your firm’s response should be sent to: Food and Drug Administration, Center for Devices and Radiological Health, Office of Compliance, Field Inspections Support Branch, White Oak Building 66, Rm. 2609, 10903 New Hampshire Ave., Silver Spring, MD 20993. Refer to CMS case #429171 when replying. If you have any questions about the contents of this letter, please contact: Daniel Walter, Chief, Foreign Enforcement Branch, at 301-796-5587 (phone) or 301-847-8139 (fax).
 
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. 
 
Sincerely yours,
/S/                                                           
Steven D. Silverman
Director
Office of Compliance
Center for Devices and
     Radiological Health

 

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