Ulrich GmbH & Co. KG 8/15/13
| || |
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
10903 New Hampshire Avenue
White Oak Building 66
Silver Spring, MD 20993
VIA UNITED PARCEL SERVICE
Mr. Christoph Ulrich
Ulrich GmbH & Co., KG
Dear Mr. Ulrich:
During an inspection of your firm located in Ulm, Germany on April 29, 2013, through May 3, 2013, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures the Pezo PEEK Cage System. Under section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. § 321(h), this product is a device because it is 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 any function of the body.
This inspection revealed that this device is 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 May 21, 2013, on behalf of your firm, concerning our investigator's observations noted on the Form FDA 483 (FDA 483), List of lnspectional 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 procedures for implementing corrective and preventive action, as required by 21 CFR 820.100(a). For example,
a) Section 5.11 of your firm's CAPA procedure (SOP-02-01-01, June 2, 2010) states, "There view of efficacy confirms that the action has led to the desired improvements and prevents or reduces any recurrence of the problem. "Four CAPA Reports (#2012-001, #2012-006, #2012-009, and 2012-016), failed to state whether the verifications/validations were effective. This is a repeat observation from the 2005 inspection.
b) Your Customer Complaints CAQ (Complaint Handling Procedure, Document Code AA-02-04-01 Rev, 04.1) ties complaints to your CAPA procedure. There was no documentation that the corrective and preventive actions for three complaint reports (#K-000454, #K-00676, and #K-00672) were effective.
The adequacy of the response dated May 21, 2013, cannot be determined at this time. Your firm provided revisedForm F-02-01-01 CAPA-KVP to include the requirement for answering the following two questions: (1) "(b)(4)" and, (2) "(b)(4)" Your firm also provided a revised work instruction Wl-02-01-01, Measures and Task Management. Although your firm promised to conduct an examination of all CAPAs and complaints over the past two years with regard to the verification/validation phase, and the carrying out of subsequent critical points, no documentation of the retrospective analysis or documentation of employee re-training on the new procedure or forms was provided.
2. Failure to establish and maintain proceduresto control the design of the deviceinorder to ensurethat specified design requirementsare met, as required by 21 CFR 820.30(a). For example:
a. The Design Validation for the Pezo PEEK Cage System included testing for (b)(4). Test Report No. 27.081219.30.677-Part 3 dated February 16 ,2009, shows the results for (b)(4); however, there is no documentation for ensuring that the devices conform to user needs and intended uses.
The adequacy of the response dated May 21, 2013, cannot be determined at this time. The response included (1) revised Form 03-01-24, which requires acceptance criteria for every test; and, (2) documentation of employee training on the revised form. These corrections are adequate for ensuring that devices conform to user needs and intended uses in the future. However, there is no documentation to demonstrate that a retrospective review of your firm's other devices was also conducted to ensure that they conform to user needs and intended uses.
b. The design project plan for the Pezo PEEK Cage System (dated April 1, 2013) includes (b)(4); however, the design plan fails to show where and how design outputs met design input requirements.
The adequacy of the response dated May 21, 2013, cannot be determined at this time. Your firm provided revisions to the Design Input Document (Form 03-03-23) which now includes a comparison with the results of the Design Outputs, and a confirmation that all points match. However, there is no documentation that your firm conducted a review of all its devices to ensure compliance with 820.30(f), or documentation of the employee training on the new procedures.
c. The Pezo PEEK Cage System (Pezo System) consists of two versions: (b)(4). The risk reduction activities for the (b)(4). However, the validation checklist indicates that validation V08 was for the (b)(4). Mr. Sven Hamich, R&D engineer, stated the validation document referenced was the incorrect validation. The correct version of the validation was presented to the FDA investigator at the close of the inspection.
The response dated May 21, 2013, appears to be adequate. Your firm explained there was a mix-up of the paperwork between the (b)(4). Your firm provided a corrected Checklist M for Risk Analysis showing the correct Pezo validation for V08.
d. The design reviews for the product idea and product conception phases of the design project for the Pezo PEEK Cage System did not indicate the outcome of the reviews.
The response dated May 21,2013, is not adequate. The response included: (1) revised design review documents for design input, design concept, design output, design transfer, design completion and validation; (2) documentation of employee training on the new review documents; and, (3) verification, and where necessary, subsequent evaluation of all technical documentation reviews (DHF) for products which are available in the market on July 31, 2013. However, the response did not include evidence of implementation of the correction and corrective action for the Summary/Outcome check boxes on the older version of the Design Review documents (MS1 and MS2), which were released January 3, 2007.
Additionally, there was no documentation that your firm reviewed the DHFs of its other devices to ensure compliance with 820.30(e).
3. Failure to define the type and extent of control 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, the Supplier Assessment Procedure (SOP-05-01-01, 03/22/2011) requires annual supplier assessments. No supplier assessments were conducted for (b)(4) for either (b)(4). This was confirmed by Mr. Thomas Fechter, Head of Purchasing.
The response dated May 21, 2013, is not adequate in that it did not address this item.
4. Failure to establish and maintain procedures for quality audits and to 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 requiredby 21 CFR 820.22. For example, your Internal Audit Procedure (SOP-02-07, May 4, 2012) requires (b)(4) to conduct (b)(4) quality audits ((b)(4)). Audits for the area of quality assurance were not conducted for (b)(4). Your firm stated that the are as of quality assurance and quality management were previously combined into one area and only one audit was conducted that covered both areas. These two areas were separated in (b)(4); however, separate audits were not conducted in (b)(4). This is a repeat observation from the 2005 inspection.
The response dated May 21, 2013, is not adequate in that it did not address this item.
Our inspection also revealed that your firm's Pezo PEEK Cage System 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 adequately develop, maintain, and implement written MDR procedures, as required by 21 CFR 803.17(a). For example, after collectively reviewing your firm's MDR procedures titled "MDR Medical Device Reporting," SOP-02-04-01, Revision 5, dated August 27, 2012, and "MDR Determination, "Wl-02-04-02, Revision 3, dated May 12, 2012, the following issues were noted:
1. Your firm's MDR procedures do 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. There are missing definitions of what your firm will consider to be a reportable event under 21 CFR Part 803. To facilitate the correct interpretation of reportable events and to assure the quality of MDR submissions, the procedure should include definitions based on 21 CFR 803.3 for the terms "become aware," "caused or contributed," and definitions for the terms "reasonably known" and "reasonably suggests," found respectively in 21 CFR 803.50(b) and 803.20(c)(1).
b. The flowchart in your firm's procedure Wl-02-04-02 "MDR Determination," Section 4.2, uses the term "cause for concern" to identify reportable events. "Cause for concern" is not a term defined by the regulation and should not be used to identify events as reportable.
2. Your firm's MDR procedures do not establish internal systems that providefor a standardized review process to determine when an event meets the criteria for reporting under this part. For example, the procedures do not have instructions for conducting a complete investigation of each event and evaluating the cause of the event.
3. Your firm's MDR procedures do not establish internal systems that provide for timely transmission of complete medical device reports. Specifically, your firm's procedure does not include instructions for how to obtainand complete the FDA 3500A form.
In addition, your firm's MDR procedures include references to baseline reporting and annual certification, which are no longer required. We recommend that all references to Baseline Reports and Annual Certification be removed from your firm's MDR procedures (see: 73 Federal Register Notice 53686, dated September 17, 2008; and Fourth Notice, Federal Register, dated March 20, 1997: Medical Device Reporting, Annual Certification, Final Rule, respectively).
We reviewed your response dated May 21, 2013, and conclude that it is not adequate because your response did not include a revised version of your firm's MDR procedures.
Given the serious nature of the violations of the Act, the Pezo PEEK Cage System devices 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 is taking steps to refuse entry of these devices into the United States, known as "detention without physical examination," until these violations are corrected. In order to remove the devices from detention, your firm should provide a written response to this Warning Letter as described below and correct the violations described in this letter. We will notify you if your firm's response appears to be adequate, and we may need to re-inspect your firm's facility to verify that the appropriate corrections and/or corrective actions have been made.
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. 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 actions (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 #407860 when replying. If you have any questions about the contents of this letter, please contact: Matthew C. Krueger, Chief, Orthopedic & Physical Medicine Devices Branch, at (301) 796-5585 or FAX (301)847-8139.
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 lnspectional 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