Natus Europe GmbH 4/19/13
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Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
| ||10903 New Hampshire Avenue|
Silver Spring, MD 20993-0002
April 19, 2013
VIA UNITED PARCEL SERVICE
Natus Europe GmbH
Robert-Koch- Str 1
Dear Mr. Mönkhoff :
During an inspection of your firm located in Planegg, Germany, on November 12, 2012, through November 15, 2012, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures Echo‑Screen devices. 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.
Our inspection revealed that the Echo-Screen 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 devices that is required by or under section 519 of the Act, 21 U.S.C. § 360i, and 21 CFR Part 803 – Medical Device Reporting.
We received a response from you dated December 05, 2012, 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. These violations include, but are not limited to, the following:
Failure to develop, maintain, and implement written MDR procedures, as required by 21 CFR 803.17. The procedure titled, “Vigilance and Recall procedure,” VA 22 Document No. 082022E0,1 dated June 18, 2010, describes a process for recalls and reportability of events to other regulatory or competent authorities and not FDA. The referenced procedure is not an MDR procedure.
We reviewed your firm’s response and conclude that it is not adequate. Your firm developed an MDR procedure titled, “Adverse Event Reporting Procedure,” Document Number QMS-000039, Rev E. After reviewing the procedure QMS‑000039, Rev E, the following issues were noted:
1. There is no evidence that your firm’s MDR procedure has been implemented. For example, there is no effective date for the procedure.
2. The procedure does not establish internal systems that provide for timely and effective identification, communication, and evaluation of events that may be subject to MDR requirements. For example:
a. The procedure includes definitions from 21 CFR 803.3, but omits the definition for the terms “reasonably known” and “reasonably suggests,” found respectively in 21 CFR 803.50(b) and 803.20(c)(1). The exclusion of these terms from the procedure may lead your firm to make an incorrect reportability decision when evaluating a complaint that may meet the criteria for reporting under 21 CFR 803.50(a).
3. The procedure does not establish internal systems that provide for timely transmission of complete medical device reports. Specifically, the following are not addressed:
a. Instructions for how to obtain and complete the FDA 3500A form.
b. The circumstances under which your firm must submit supplemental or follow-up reports and the requirements for such reports.
c. The address for where to submit MDR reports: FDA, CDRH, Medical Device Reporting, P.O. Box 3002, Rockville, MD 20847-3002.
Also the procedure references baseline reports. Baseline reports are no longer required and all references to a Baseline Report should be removed from your firm’s MDR procedure (see: 73 Federal Register Notice 53686, dated September 17, 2008).
If your firm wishes to submit MDR reports via electronic submission it can follow the directions stated at the following URL:
If your firm wishes to discuss MDR reportability criteria or to schedule further communications, it may contact the Reportability Review Team by email at ReportabilityReviewTeam@fda.hhs.gov
Also, 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.
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 action (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. Please provide a translation of documentation not in English to facilitate our review.
In addition, FDA has noted nonconformances with regards to section 501(h) of the Act, 21 U.S.C. § 351(h), which are deficiencies within your firm’s quality system pertaining to current good manufacturing practice requirements specified in the Quality System regulation found at 21 CFR Part 820. These nonconformities include, but are not limited to, the following:
1. Failure to establish and maintain procedures for implementing corrective and preventive action, as required by 21 CFR 820.100(a).
For example, your firm’s procedure, “Corrective and Preventive Action Including Customer Complaints,” VA14, Document No. 082014, does not include:
a. A complete listing of sources of quality data analyzed in order to identify existing and potential causes of nonconforming product or other quality problems.
b. Requirements for the verification or validation of the corrective and preventive action to ensure that such action is effective and does not adversely affect the finished device.
Your firm’s response to this observation appears to be adequate. Your firm replaced the procedure, “Corrective and Preventive Action Including Customer Complaints,” VA 14, with the Natus Corporate “Corrective and Preventive Action Procedure,” QMS-000086, revision B, which includes a complete listing of sources of quality data analyzed for existing and potential causes and the requirements for the verification or validation of the corrective and preventive action. Additionally, your firm provided copies of the new procedure and training records on the new procedure.
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)(3). The procedures shall ensure that complaints are evaluated to determine whether the complaint represents an event that is required to be reported to FDA under Part 803, Medical Device Reporting.
For example, your firm’s “Corrective and Preventive Action Including Customer Complaints” procedure, VA14, Document no. 082014, is used to adopt, implement, and document appropriate corrective and preventive actions to eliminate the cause of errors or non-conformances from customer complaints or from internal sources. However, the procedure does not include requirements to ensure that all complaints are evaluated to determine whether the complaint should be filed as a Medical Device Report (MDR).
Your firm’s response to this observation appears to be adequate. Your firm replaced the procedure “Corrective and Preventive Action Including Customer Complaints,” VA 14, with the Natus Corporate “Corrective and Preventive Action Procedure,” QMS-000086, revision B, to include requirements to evaluate all complaints as reportable events. In addition, your firm included a definition for “reportable events” in the “Adverse Event Reporting,” QMS-000039, procedure. Your firm included evidence that employees were trained on the revised procedure. Also, your firm conducted a retrospective review of all complaints from 2011 and 2012 for the Echo-Screen product line using the new Complaint Handling procedure, QMS-000050, and all complaints were found to have been properly evaluated for MDR reportability.
3. Failure to document Corrective and Preventive Action activities, as required by 21 CFR 820.100(b).
For example, the reports, (b)(4), initiated September 13, 2011, (b)(4), initiated May 02, 2011, (b)(4), initiated January 04, 2012, (b)(4), initiated August 02, 2012, (b)(4), initiated August 20, 2012, (b)(4), initiated August 22, 2012, (b)(4), initiated June 18, 2012, and (b)(4), initiated October 25, 2012, did not have complete documentation of all activities performed, including implementation of all corrective actions and verification and validation of the corrective action.
We reviewed your firm’s response and conclude that it is not adequate. Your firm noted that it has adopted the (b)(4), (b)(4), to replace CAPA forms. In addition, your firm trained employees on the use of the CAPA form in (b)(4) in order to resolve the inadequate documentation issue. Also, your firm provided evidence of implementation, including an example of a completed in-process CAPA form using (b)(4) and training records. However, your firm has not provided a plan and evidence of the systemic corrective action, including retroactive review of CAPA reports for proper documentation.
4. Failure to maintain a record of the investigation by the formally designated unit identified in 21 CFR 820.198(a), as required by 21 CFR 820.198(e).
For example, your firm’s “Corrective and Preventive Action Including Customer Complaints” procedure, VA14, Document no. 082014E, does not ensure that the date the complaint was received, the dates and results of the investigation, and any reply to the complainants are recorded and retained in the complaint records when an investigation into the failure is conducted.
Your firm’s response to this observation appears to be adequate. Your firm stated that it replaced the procedure “Corrective and Preventive Action Including Customer Complaints,” VA14, with Natus Corporate Complaint Handling Procedure, QMS-000050, revision G, and provided a copy of the new procedure and new Complaint Form, 089-144-02, which captures required elements of the new complaint procedure. The form now includes sections for receiving, investigating, and documenting the results of investigation. Additionally, your firm trained employees on the new form and provided evidence of implementation.
5. Failure to document the disposition of nonconforming products and rework activities, as required by 21 CFR 820.90(b).
For example, your firm’s procedure for nonconforming products, “Controlling Defective Products,” VA 13, Document no. 082013, and the procedure for incoming inspection, “Testing and Labeling of Products,” VA 10, Document no. 082010, do not include the requirements to ensure that the disposition of nonconforming devices and probes are documented. Additionally, your firm’s procedure for nonconforming products, “Controlling Defective Products,” VA 13, Document no. 082013, section 7.4, states that defects that are to be repaired immediately by the same worker are documented and immediately attended to. However, your firm did not record the rework activities present in Supplier Corrective Action Requests (SCARs) (b)(4), (b)(4), (b)(4), (b)(4), and (b)(4).
We reviewed your firm’s response and conclude that it is not adequate. Your firm replaced the procedure, “Controlling Defective Products,” VA 13, with Natus Corporate Nonconforming Product procedure, QMS-000158, revision B, which include requirements for disposition and documentation of nonconforming material. In addition, the procedure includes the requirement to review nonconformance records to ensure that rework activities are properly documented. Also, form number 089-143-01, “Non-conformance Report,” was created and lists all possible dispositions for nonconforming product. Your firm provided a copy of the procedure, non‑conformance report form, work instructions, and forms governing rework of the Echo-Screen and probes. In addition, your firm provided evidence that employees were properly trained on this procedure and forms. However, your firm has not provided a plan and evidence of the systemic corrective action, including retroactive review of previous rework and non-conforming records.
6. Failure to use calibration standards for inspection, measuring, and test equipment that are traceable to national or international standards, or if national or international standards are not practical or available, to independently reproducible standards or established and maintained in‑house standards, as required by 21 CFR 820.72(b)(1). For example, your firm’s calibration procedures, “Test Equipment Monitoring,” VA 11, Document no. 082011E, does not ensure that the calibration of test equipment links to a national or international standard.
Your firm’s response to this observation appears to be adequate. Your firm revised the procedure, “Test Equipment Monitoring,” VA 11, to state that all test equipment must be calibrated to or verified in defined intervals or, before use, to international or national calibration standards. Your firm provided a copy of the revised procedure and training records of affected employees on this procedure. In addition, your firm will conduct audit of all calibrated equipment used in production of the Echo-Screen by December 31, 2012.
7. Failure to establish 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, your firm’s quality audit procedure, “Internal Quality Audits,” VA 17, Document no. 082017, Version 7, Section 6.4, requires that an (b)(4) audit plan approved (b)(4) to ensure that all parts of the quality management (QM) system of the Natus Europe GmbH and all relevant departments concerned are subject to an internal quality audit at least (b)(4). However, review of quality audit plans for (b)(4) revealed that no audit of the Quality Management/Documentation was not conducted in (b)(4).
The adequacy of your firm’s response cannot be determined at this time. Your firm replaced the procedure “Internal Quality Audits,” VA 17 with Natus Corporate Internal Quality Audit Procedure, QMS-000013, revision D, which includes an updated audit plan via documentation control process in order to accommodate staffing changes. Also, your firm provided copies of the new procedure and evidence that employees were properly trained on this procedure. Additionally, your firm noted that corporate audit of all corrective actions will be completed by (b)(4). However, your firm did not submit for review documentation demonstrating that the corporate audit was completed.
8. Failure to establish and maintain procedures to control labeling activities, as required by 21 CFR 820.120.
For example, the firm’s labeling procedure, “Test and Labeling of Products,” VA 10, lacked requirements for:
a. Adequately controlling labeling and packaging operations to prevent labeling mix-ups.
b. Ensuring that labeling was sufficiently examined by a designated individual for accuracy.
c. Ensuring that the Device History Record (DHR) includes records of approval and release of device labeling, including the date and signature of the examiner, and for ensuring that labels and labeling used for each finished product, lot, or batch are sufficiently documented and kept in the DHR.
Additionally, DHRs reviewed did not include documentation of the review/approval of the labeling used or documentation of the primary identification labels applied to the devices and probes.
The adequacy of your firm’s response cannot be determined at this time. Your firm created a new work instruction, “Work Instruction Labeling Hearing,” 001AA10E, version A, in order to define the requirements for control of labeling and DHR creation. The work instruction states the requirements to control labeling and packaging information, ensure that labeling is examined by designated individual for accuracy, and that the records of labeling and labeling checks are included in the DHR. In addition, your firm created Work Instruction “Device History Record,” 001AA11E, in order to ensure that records of approval and release of device labeling, documentation of labeling, and independent QA review and approval of DHRs are completed. Your firm provided copies of the work instructions, forms, and training records of all affected employees on the new work instructions and forms. However, your firm did not provide evidence of implementation of the corrective action.
9. 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 part 820 and the manufacturer’s established quality policy and objectives. The dates and results of quality system reviews shall be documented, as required by 21 CFR 820.20(c).
For example, your firm’s procedure, “Management Review,” VA 21, Document no. 082021, Version 02, Section 6.2, requires that management reviews be performed at least (b)(4). However, no management review attendance records were available for a management review meeting held in (b)(4).
Your firm’s response to this observation appears to be adequate. Your firm replaced the procedure “Management Review,” VA 2,1 with Natus Corporate Management Review Procedure, QMS-000009, revision B and created a new attendance record form, Form 089-146-02, “Management Review Attendance Record Form,” in order to document Management Review attendance. Also, your firm provided evidence that appropriate training on the new procedure was conducted. Your firm provided copies of the new procedure, forms, and training records, which appear to be adequate. Finally, your firm conducted Management Review on (b)(4), using the new attendance record Form and provided evidence of implementation.
Your firm’s response to this letter should be sent to: Food and Drug Administration, Center for Devices and Radiological Health, Office of Compliance, Field Operations Branch, White Oak Building 66, Room 2609, 10903 New Hampshire Ave., Silver Spring, MD 20993. Refer to CMS case # 394336 when replying. If you have any questions about the contents of this letter, please contact: Ronald L. Swann, Chief, Dental, Ear, Nose, Throat, and Ophthalmic Device Branch at 301-796-5770or (fax) 301-847-8137.
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.
Steven D. Silverman
Office of Compliance
Center for Devices and
Dr. D. Christopher Chung, MD
Vice President, Medical Affairs, Quality and Regulatory
Natus Medical Incorporated
1501 Industrial Road
San Carlos, California 94070