Inspections, Compliance, Enforcement, and Criminal Investigations
Osypka Medical GmbH 3/7/12
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
|10903 New Hampshire Avenue|
Silver Spring, MD 20993
Mar 7 2012
VIA UNITED PARCEL SERVICE
Mr. Thilo Thuemecke
Director of Operations
Osypka Medical GmbH
Dear Mr. Thuemecke:
During an inspection of your firm located in Berlin, Germany,on November 28, 2011, through December 01, 2011, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures external pacemakers and cardiac monitoring devices (impedance plethysmographs). 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 they are intended to affect the structure or function of the body.
The 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 you, on behalf of your firm, dated December 9, 2011, concerning our investigator’s observations noted on the Form FDA 483 (FDA 483), List of Inspectional Observations, that 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:
1. 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: your firm’s design-change procedure does not address the need for design verification or validation, when appropriate. The investigator reviewed ticket #19, which identified the need for a new component due to the obsolescence of that component, by the current supplier for the P203H and P300 pacemaker devices. (b)(4) No verification or validation activities were identified and documented in ticket #19 for this design change and the ticket was approved and closed.
We reviewed your response and conclude that it is not adequate. Your firm’s response did not include documentation of the validation performed on the new series of production circuit boards; a copy of the (b)(4) procedure; or documentation to verify that ticket #19 was reopened, to support the implementation of these actions. Additionally, your firm has not provided a description and documentation of implementation of a systemic corrective action to include the review of other design changes and production changes to ensure that proper verification and validation activities have been completed according to your firm’s procedures.
2. Failure to establish and maintain adequate procedures for implementing corrective and preventative action, to include requirements for analyzing processes, work operations, concessions, quality audit reports, quality records, service records, complaints, returned product, and other sources of quality data to identify existing and potential causes of nonconforming products, or other quality problems, as required by 21 CFR 820.100(a)(1).
For example: your firm’s corrective and preventative action procedure does not include service reports as a data source for potential corrective and preventative actions.
The adequacy of your firm’s response cannot be determined at this time. Your firm plans on updating both the CAPA procedure and form to include (b)(4) for corrective and preventive actions. Your firm also stated that it will (b)(4). Your firm did not provide documentation to support the implementation of these actions.
3. 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).
For example: your firm failed to review complaints to determine whether the complaint represents an event which is required to be reported to FDA under 21 CFR 803, Medical Device Reporting. Your firm states that its sister facility, Osypka Medical, Inc. (OMI), in the U.S., is responsible for evaluating complaints for the need to be filed as medical device reports. However, your firm’s agreement with its sister facility does not specify that OMI is responsible for evaluating complaints for the need to be filed as medical device reports.
The adequacy of your firm’s response cannot be determined at this time. The response states that the agreement between your firm and Osypka Medical, Inc. (OMI), will be updated to reflect responsibilities for timely and effective identification, communication, and evaluation of device-related events that may be subject to medical device reporting. Also, the response stated that your firm will update its [redacted as b(4)] to reflect these responsibilities. Your firm has not provided documentation to support the implementation of these actions, including the revised procedure, training on the revised procedure, and the updated agreement with OMI.
During the inspection and discussion with your firm, it was communicated and documented in Observation 6, part B, that your firm’s customer complaint handling procedures do not require that service reports be reviewed for potential customer complaints. In your response dated December 9, 2011, you state that an updated layout of your firm’s service report form will be completed by December 31, 2011, which will include (b)(4) There is no requirement under 21 CFR 820.198 that specifically states that service records need to be reviewed as complaints. To provide clarification, 21 CFR 820.200(c) states that each manufacturer who receives a service report that represents an event which must be reported to FDA under part 803 (Medical Device Reporting) shall automatically consider this report a complaint and shall process it in accordance with the requirements of 21 CFR 820.198.
4. Failure to promptly remove all obsolete documents from all points of use or otherwise prevent from unintended use, as required by 21 CFR 820.40(a).
For example: the 2011 calibration of stopwatch number 0611 used calibration work instruction version 1.0 to perform the calibration. The latest calibration work instruction version for that instrument is version 1.1, which had been used in 2010 to calibrate the same stopwatch. Your firm stated that the work instructions for calibration (b)(4) Your firm states that its software does not have the capability of moving the obsolete work instructions to a separate folder so that they can not be accessed and used for calibration activities.
The adequacy of your firm’s response cannot be determined at this time. Your firm confirms that the software which is used for the calibration of measuring equipment contains both the old and new version of the calibration plan for (b)(4). Your firm states that the tester chose the wrong calibration plan by mistake, leading to more testing than needed according to the new plan. Your firm states that it will delete all obsolete calibration plans from the calibration software so that, in the future, the tester can only chose the current test plan for each piece of equipment needing calibration. Additionally, your firm will re-train the tester of the measurement equipment. Your firm has not provided documentation to support the implementation of these actions.
5. Failure to establish adequate 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: the investigator reviewed the internal audit plans for 2009 and 2010, which include requirements for audits of the packaging, shipping, and storage area to include section 7.5.4 of the ISO requirements. When the internal documentation for 2009 and 2010 was reviewed, it showed that your firm did not cover section 7.5.4 of the ISO requirements as defined in your firm’s audit plan.
We reviewed your firm’s response and conclude that it is not adequate. The response states that internal audits are documented by (b)(4). Your firm recognizes that section 7.5.4 (Property of Customers) was part of the questionnaire for internal audit number 04, but this section was not filled in by mistake in 2009, 2010, and 2011. Your firm states that it will repeat internal audit number 04 for 2011 to include section 7.5.4 and retrain its internal auditors accordingly. Your firm did not provide documentation to support the implementation of the actions taken. Additionally, your firm has not provided a description and documentation of implementation of a systemic corrective action to include the review of all audit reports and questionnaires to ensure that all sections were completed as required.
Our inspection also revealed that your firm’s external pacemakers and cardiac monitoring 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 violations include, but are not limited to, the following:
Failure to develop, maintain, and implement written Medical Device Reporting (MDR) procedures, as required by 21 CFR 803.17.
For example: your firm includes provisions for vigilance reporting in its complaint handling procedures; however, when asked by the investigator if the firm had procedures for medical device reporting, you indicated that the firm did not have such procedures.
The adequacy of your firm’s response cannot be determined at this time. Your firm states that the agreement between itself and OMI in the U.S. will be updated to reflect the responsibilities for timely and effective identification, communication, and evaluation of device-related events that may be subject to MDR requirements. Your firm states that it will update its (b)(4) to reflect these responsibilities. Your firm also states that OMI is responsible for the devices that it sells in the U.S., including the service and repair of those devices. Your firm also states that OMI has established procedures for complaints and MDRs. Your firm has not provided documentation to support these statements.
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. 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, 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.
Your firm’s response should be sent to: Food and Drug Administration, Center for Devices and Radiological Health, Office of Compliance, Field Operations Branch, White Oak Building 66, Rm 2609, 10903 New Hampshire Ave., Silver Spring, MD 20993. Refer to CMS case #271536 when replying. If you have any questions about the contents of this letter, please contact: Joshua Simms at 301-796-5599.
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