| Public Health Service Food and Drug Administration |
| 10903 New Hampshire Avenue Silver Spring, MD 20993 |
Department of Health and Human Services
December 7 2010
WARNING LETTER
VIA UPS EXPRESS
Mr. Volker Bertram
President and CEO
VBM Medizintechnik GmbH
Einsteinstrasse 1
Sulz Am Neckar
Germany
Dear Mr. Volker Bertram:
During an inspection of your firm located in Sulz Am Neckar, Germany on June 7 through June 10, 2010, investigator(s) from the United States Food and Drug Administration (FDA) determined that your firm manufactures the QuickTrach Sterile Tracheostomy device, the QuickTrach II Sterile Tracheostomy Device, the Jet Ventilation Catheters (JVC), and the Control Inflator Device. 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 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 Mr. Volker Bertram, President and CEO dated June 24, 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 document in the design history file the results of the design validation, including identification of the design, method(s), the date, and the individual(s) performing the validation, as required by 21 CFR 820.30(g). For example, you had no documentation in the design history file of the design validation activities performed for the QuickTrach II project where an inflatable cuff was added to the QuickTrach I design.
Your response dated 06/24/2010 is not adequate. The response states that future design validation results will be archived in the Design History File. Your response does not address why the required documents were not contained within the Design History File to begin with. Your response did not describe how you propose to assure that design validation results will be archived within the design history file, either via a process or procedure. Your response did not address the review of Design History Files to determine if additional required documents were missing. You promised to correct this observation by 11/30/2010.
2. Failure to document in the design history file the results of design verification, including identification of the design, method(s), the date, and the individual(s) performing the verification, as required by 21 CFR 820.30(f). For example, you had no documentation in the design history file of the design verification activities performed for the QuickTrach II project where an inflatable cuff was added to the QuickTrach I design.
Your response dated 06/24/2010 is not adequate. Your response states that QS Form 53 will be used to document verification activities and that Form 53 will be included within the Design History File. Your response does not address why the required documents were not contained within the Design History File to begin with. Your response did not address the review of Design History Files to determine if additional required documents were missing. You promised to correct this observation by 11/30/2010.
3. Failure to establish and maintain adequate procedures for the identification, documentation, validation or where appropriate verification, review, and approval of design changes, as required by 21 CFR 820.30(i). For example, CAPA Nr. 49-09 involved the sticking of silicone tubing used in Control Monitors when the devices remained out of use for 3-6 months. In reaction, you implemented a design change (the addition of a talcum coating to the tubing) but did not validate or verify that the addition of the talcum coating would prevent the sticking of the silicone tubing over time.
Your response dated 06/24/2010 to FDA 483 observation 8 was assessed and is not adequate. Your response did not include an assessment of your design change control activities related to the observation.
4. Failure to establish and maintain adequate procedures for verifying or validating corrective and preventive action to ensure that such action is effective, as required by 21 CFR 820.100(a)(4). For example, CAPA Nr. 49-09 involved the sticking of silicone tubing used in Control Monitors when the devices remained out of use for 3-6 months. In reaction, you implemented a design change (the addition of a talcum coating to the tubing). Your procedure entitled “8.5.2 Corrective and Preventive Actions” did not ensure that the corrective action was verified or validated as effective in preventing the sticking of silicone tubing in distributed products.
Your response dated 06/24/2010 is not adequate. You revised your CAPA procedure to include a verification/validation step into the process between “Defining the corrective and preventive actions” and “Implementation of the corrective and preventive actions” (you provided a copy of the revised procedure in both German and English). You also revised QS Form 92 to assure that verification/validation documents will be archived within the CAPA file in the future (you provided a copy of this revised form in both German and English). You provided a copy of the correspondence to the responsible VBM staff notifying them of these changes to the CAPA procedure and QS Form 92. Your response did not address why the CAPA procedure was deficient to begin with or whether other CAPA files were reviewed to ensure necessary verification or validation activities were complete and documented. You promised to correct this observation within 30 days.
5. Failure to maintain complaint files and 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, your complaint handling procedure does not define the term “complaint” in accordance with 21 CFR 820.3(b); rather it defines complaints by the product warranty status.
Your response dated 06/24/2010 is not adequate. Your response states that the 8.5.1. Complaint/Repair procedure has yet to be revised to reflect the QS regulation definition of the term “complaint”. Your response did not address the identification of complaints from your existing population of repairs or why the complaint procedure was deficient to begin with. You promised to correct this observation by 11/30/2010.
6. Failure to adequately document Corrective and Preventive Action activities and/or results, as required by 21 CFR 20.100(b). For example:
A. Closed CAPA files, CAPA Nr. 04-09; CAPA Nr. 49-09; CAPA Nr. 56-09; and CAPA Nr. 55-2007 did not include documentation of the verification or validation of the effectiveness of the corrective/preventive actions.
B. CAPA Nr. 04-09 did not reference or include documentation of a requested supplier investigation into the failure of a JVC catheter due to separation of the Teflon cannula from the luer.
The adequacy of your response dated 06/24/2010 cannot be determined at this time.
7. The disposition of nonconforming product is not documented, as required by 21 CFR 820.90(b)(1). For example, the disposition of nonconforming returned product was not documented for three of the eleven complaints reviewed (Complaint No.s 2007RP0662, 2007RK0138, and 2007RK0315).
Your response dated 06/24/2010 is not adequate. Your response states a block has been added to QS Forms 83a, 83b, 24 and 56 to document the disposal of nonconforming product and that responsible individuals were trained. Your response did not address why procedures used to document the disposition of nonconforming product were deficient to begin with or whether all potential dispositions were reviewed to ensure they are documented appropriately. Your response did not include a revised nonconforming product procedure that defined the responsibility for review and the authority for the disposition of nonconforming product.
8. Failure to establish and maintain procedures to ensure that participants at each design review include representatives of all functions concerned with the design stage being reviewed and an individual(s) who does not have direct responsibility for the design stage being reviewed, as well as any specialists needed, as required by 21 CFR 820.30(e). For example, your design control procedures did not include requirements for ensuring that an individual without direct responsibility for the design phase being reviewed is included in its design review meetings.
Your response dated 06/24/2010 is not adequate. Your response states that the [(b)(4)] would be the independent audit authority effective 06/17/2010 as described in QS Form 66 [(b)(4)]. You changed QS Form 88 Revision 10 to reflect that the [(b)(4)] is now the independent authority for design control phases 1-6. In addition, you removed the field “Not Applicable” previously found on QS Form 88. Your response did not address why the design review procedure was deficient to begin with and whether systemic corrective action was necessary. You promised to correct this observation within 30 days.
9. Sampling plans are not based on a valid statistical rationale, as required by 21 CFR 820.250(b). For example, as part of corrective actions implemented to address the separation of the cannula from the flange of Jet Ventilation Catheters (as described in CAPA 55-2007), [(b)(4)] devices per lot are sampled for torque testing. Product lot sizes vary from [(b)(4)] to [(b)(4)] devices. No valid statistical rationale for this sampling plan was documented.
The adequacy of your response dated 06/24/2010 cannot be determined at this time.
10. Failure to establish procedures to control labeling activities, as required by 21 CFR 820.120. For example, no count or reconciliation of labels printed, labels applied or labels scrapped was documented for sterilized lots of QuickTrach II, as specified in the packaging Work Instruction entitled Verpackungsvorschrift MedicpackerS-004Z02.
The adequacy of your response dated 06/24/2010 cannot be determined at this time.
11. Training is not documented as required by 21 CFR 820.25(b). For example, there is no documentation of the training of responsible personnel with respect to the following changes implemented as part of corrective or preventive actions:
A. The new inspection push test implemented in work instruction H3-015Z08 as per CAPA 04-09
B. The new specification implemented in work instruction H3-056Z06 as per CAPA 56-09
C. The new torque testing implemented in work instruction H3-015Z08 as per CAPA 55-2007.
The adequacy of your response dated 06/24/2010 cannot be determined at this time.
Our inspection also revealed that your the QuickTrach Sterile Tracheostomy device, the QuickTrach II Sterile Tracheostomy Device, the Jet Ventilation Catheters (JVC), and the Control Inflator Device 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:
12. Failure to report to FDA no later than 30 calendar days after the day that you received or otherwise became aware of information, from any source, that reasonably suggests that a device that you have marketed may have caused or contributed to a death or serious injury, as required by 21 CFR 803.50(a)(1). For example, two of the 11 complaints reviewed involved complaints of failures of your Jet Ventilation Catheter (JVC), which required subsequent treatment of the patient as a result of the failure, as described below:
A. Complaint Archive Nr. 08/08 - involved a failed intubation attempt on a 78 year old male patient with the JVC due to a break at the juncture of the cannula with the hub of the device. The defective JVC device was removed and the patient was intubated using a different device. You could not produce any documentation to the investigator that demonstrated that you had notified FDA of this failure. Your justification for not reporting to FDA was that no devices with the same lot number were distributed to the U.S. however; your investigation into the failure did not identify the failure as specific to only one lot.
B. Complaint Archive Nr. 05/08 - involved a reported failure of a JVC catheter during intubation of a patient under anesthesia due to twisting of the inner catheter leading to occlusion of the device. The defective JVC device was removed and the patient was intubated using a different device. You could not produce any documentation to the investigator that demonstrated that you had notified FDA of this failure. Your justification for not reporting to FDA was that no devices with the same lot number were distributed to the U.S. however; your investigation into the failure did not identify the failure as specific to only one lot.
Your response dated 06/24/2010 appears to be adequate.
13. Failure to establish and maintain MDR event files as part of your complaint file, under Part 820 of this chapter, if the firm prominently identifies these records as MDR reportable events, as required by 21 CFR 803.18(e). For example, the results of the evaluation of each event are not documented and maintained in the manufacturer’s MDR event file. Specifically for Complaint Archive Nr. 05/08, you tested and retained samples of the JVC catheter from different lots to verify that the retained devices met the specifications for pull and torque testing of the joint. The investigator noted that the test report results of the testing performed were not located in the complaint file. Subsequently, you provided the investigator with a notebook page which documented the testing that was performed, and it was translated from German into English.
Your response dated 06/24/2010 is not adequate because you did not discuss how you propose to prominently identify the MDR event files (as part of your complaint file) as MDR reportable events. You promised to correct this observation within 30 days.
Given the serious nature of the violation(s) of the Act, the QuickTrach Sterile Tracheostomy device, the QuickTrach II Sterile Tracheostomy Device, the Jet Ventilation Catheters (JVC), and the Control Inflator Device manufactured by your firm are subject to refusal of admission under section 801(a) of the Act, 21 U.S.C. § 381(a), in that they appear to be adulterated. As a result, FDA may take steps to refuse these products, known as "detention without physical examination," until these violations are corrected. In order to remove the devices from detention, you should provide a written response to this Warning Letter as described below and correct the violation(s) described in this letter. We will notify you if your response is adequate, and we may need to re-inspect your facility to verify that the appropriate corrections have been made.
Also, U.S. 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. Please provide a translation of documentation not in English to facilitate our review.
Your response should be sent to: Charles Cathlin, 10903 New Hampshire Ave., Silver Spring, MD 20903.If you have any questions about the content of this letter please contact: Charles F. Myers at 301-796-5619 or fax 301-847-8128.
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 FDA. 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.
Sincerely yours,
/S/
Steven D. Silverman
Director
Office of Compliance
Center for Devices and
Radiological Health
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