Inspections, Compliance, Enforcement, and Criminal Investigations
Ulrich GmbH & Co. KG 30-Aug-05
Department of Health and Human Services
| Public Health Service |
Food and Drug Administration
|Center for Devices and Radiological Health |
2098 Gaither Road
Rockville, MD 20850
August 30, 2005
VIA FEDERAL EXPRESS
Mr. Heiner Ulrich
Ulrich GmbH & Co. KG
Dear Mr. Ulrich:
During an inspection of your firm located in Ulm, Germany, on April 11 through 14, 2005, our investigator determined that your firm manufactures spinal implants and associated accessories. These products are devices within the meaning of section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act) (21 U.S.C. 321(h)).
This inspection revealed that these devices appear to be 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 (CFR), Part 820. Significant violations include, but are not limited to, the following:
1. Failure to establish and maintain adequate procedures for implementing corrective and preventive action (CAPA), as required by 21 CFR 820.100(a). For example the CAPA procedure lack requirements to:
a) Analyze quality data (complaints, device returns and in-house rejects) to identify existing and potential causes of nonconforming product, or other quality problems.
b) Verify or validate the corrective and preventive action to ensure that such action is effective and does not adversely affect the finished device .
c) Employ appropriate statistical methodology to detect recurring quality problems.
d) Submit relevant information on identified quality problems, as well as corrective and preventive actions, for management review.
2. Failure to document corrective and preventive action activities, such as, investigations of nonconformities, actions necessary to correct or prevent recurrence of nonconforming product and other quality problems, and dissemination of information about quality problems or nonconforming product to responsible parties, as required by 21 CFR 820.100(b). For example:
a) A review of data on the number of rejected spinal implants in the production area revealed that in 2004 one lot [redacted] had high rejection rate; 49 of the 50 implants were rejected because the thread area of the implant did not meet specification. There was no documented CAPA item for this event and no documented investigation into the cause of the 49 nonconformities in this lot.
b) Complaint # [redacted], concerning a VBR spinal implant disclosed the surface of the: implant had been laser marked with the incorrect height. R&D determined that the device could still be used and the incorrectly labeled device was returned to inventory with no further corrective or preventive action to address the nonconformity.
3. Failure to adequately validate a process that cannot be fully verified by subsequent inspection and test, as required by 21 CFR 820.75(a). For example the process validation documentation for the ultrasonic cleaning process utilizing [redacted], lacks information to document that implants were cleaned according to the validation test plan using worst case conditions.
4. Failure to adequately establish and maintain process control procedures that describe any process controls necessary to ensure conformance to specifications, as required by 21 CFR 820.70(a). For example, there are no written instructions for performing the First Piece Inspection of [redacted] machined spinal implants.
5. Failure to establish and maintain adequate procedures for acceptance of incoming product by failing; to inspect, test, or otherwise verify incoming product conforms to specified requirements, as required by 21 CFR 820.80(b). For example the reliability of the Certificates of Analysis (COA) showing the chemical and mechanical properties for stainless steel used to fabricate surgical instruments were not confirmed in order to verify that material specifications were truly met.
6. Failure to establish adequate procedures for quality audits, as required by 21 CFR 820.22. For example, the procedure does not require:
a) Documentation of re-audits dates,
b) The auditor be independent of the matters being audited,
c) Audits be conducted by trained individuals, and
d) A nonconformity report to be completed when a deficiency is identified during an audit.
7. Failure to establish and maintain adequate procedures to control all documents that are required by 21 CFR 820, as required by 21 CFR 820.40. For example, when a document change is required, the person from the QA management can enter the document change into the [redacted] (Quality Management Software), making the change: directly on the affected document. However there is no other existing record of the change that is maintained describing the reason for the change, description of change, and the final printed document lacks the signature of the approving official. Additionally, there is no clear tracking system to show what departments were affected by this change, if all affected departments received the revised document, and if the previous revised document had been removed.
8. Failure to establish adequate procedures to define how management with executive responsibility is to review the suitability and effectiveness of the quality system, as required by 21 CFR 820. 20(c). For example, the procedures do not require documentation of the management review dates and demonstrate that Part 820 requirements were met in that there are no requirements for management to review data pertaining to recurring quality problems, such as rejects, found in production and final Quality Control areas.
The above stated inspection also revealed that these devices are misbranded under section 502(t)(2) of the Act (21 U.S.C. 352(t)(2)), in that you your firm failed to furnish material or information as required under section 519 of the Act and regulations implementing that section at Title 21 Code of Federal Regulations (21 CFR), Part 803 - Medical Device Reporting (MDR). More specifically your firm failed to develop adequate Medical Device Reporting procedures, as required by 21 CFR 803.17. For example your procedure does not:
have a provision for the timely submission of adverse events
define certain terms such as malfunction and serious injury
identify the criteria for determining when to report an adverse event
This letter is not intended to be an all-inclusive list of deficiencies at your facility. It is your responsibility to ensure compliance with applicable laws and regulations administered by FDA. The specific violations 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 underlying problems in your firm's manufacturing and quality assurance systems. You should investigate and determine the causes of the violations, and take prompt actions to correct the violations and to bring your products into compliance.
We received a response from you dated May 20, 2045, concerning our investigator's observations noted on the FDA 483. We have reviewed your response and have concluded that the response is not adequate. Not all issues identified by the investigator were completely addressed in this response. With regards to the issue of an adequate Corrective and Preventive Action procedure, please explain the nature of the decision on the CAPA form where the employee is allowed to check Yes or No on verification or validation of the CAPA item. The form appears to imply there is an option for not verifying or validating a CAPA item. If this is the case, the form is inadequate. Verification or validation of a CAPA item is a requirement of the regulation and the form would need to be modified accordingly.
With regards to the issue of adequate documentation of process validation for the ELMA Xtr Ultrasonic Cleaner, please provide an English version of the final validation protocol and test results.
With regards to the issue of adequately establishing written procedures for conducting first piece inspection of the CNC machine, please provide a list of all components manufactured using the CNC machine subject to first piece inspections. Additionally for each component subject to first piece inspection, please explain which of the dimensions documented on the component's engineering print are to be measured during first piece inspection and if the actual measurement value is documented or if your firm intends to document only that the measured dimensions were within specification on the component's engineering print.
With regards to the issues of adequate internal audit and management review procedures, please provide English versions of the revised internal audit and management review procedures.
With regards to the Inadequate MDR procedures, FDA recommends that your firm consider utilizing the services of a qualified consultant to assist in the development of adequate MDR procedures that address all the requirements of the MDR regulation, such as timely reporting, documentation and record keeping, five and thirty day reporting, supplemental MDR reports, event files, standardized review process and when not to file a report.
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 violations, or similar violations, from occurring again. Include all documentation of the corrective action you have taken. If you plan to make any corrections in the future, include those plans with your response to this letter as well. If the documentation is not in English, please provide a translation to facilitate our review.
Your response should be sent to the Food and Drug Administration, Center for Devices and Radiological Health, Office of Compliance, Division of Enforcement B, Orthopedic, Physical Medicine and Anesthesiology Devices Branch, 2098 Gaither Road, Rockville, Maryland 20850 USA, to the attention of William MacFarland.
If you need help in understanding the contents of this letter, please contact William MacFarland at the above address or at (240) 276-0120 or FAX (240) 276-0129.
Timothy A. Ulatowski
Center for Device and Radiological Health