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U.S. Department of Health and Human Services

Inspections, Compliance, Enforcement, and Criminal Investigations

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coLigne AG 17-Oct-07

Department of Health and Human Services' logoDepartment of Health and Human Services

Public Health Service
Food and Drug Administration

 

9200 Corporate Boulevard
Rockville, Maryland 20850


OCT 17 2007

WARNING LETTER


VIA FEDERAL EXPRESS

Mr. Robert B. Lange
Chief Executive Officer
coLigne AG Utoquai 43
CH-8008 Zurich
Switzerland

Dear Mr. Lange:

During an inspection of your firm located in Zurich, Switzerland, on May 14 through 17, 2007, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures the GII Spinal Fixation System, which is intended to provide immobilization and stabilization of spinal segments in skeletally mature patients as an adjunct to fusion in the treatment of the acute and chronic instabilities or deformities of the thoracic, lumbar, and sacral spine. 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 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, dated June 22, 2007, from Dr. Dietmar Schaffarczyk, IACAPA Assistant, of your firm, concerning our investigator's observations noted on the Form FDA 483, List of Inspectional Observations, that was issued to you on May 17, 2007. 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 ensure that formal documented reviews of the design results are planned and conducted at appropriate stages of the device's design development, as required by 21 CFR 820.30(e). Specifically, design reviews were not performed during the design process for the GII Spinal Fixation System.

Your firm's June 22, 2007, response letter appears to be inadequate. During the inspection, your firm's management was unable to provide any record of design reviews for the GII Spinal Fixation System design project. Your firm's response indicates that design review activities are now conducted for the following stages throughout the product life cycle:

[redacted] For each product development phase identified, coLigne AG conducts appropriate design review activities using evidence organized according to FDA and ISO requirements. Each review now includes an agenda, minutes, participants, time, and reason for the review.

An individual without direct responsibility for the design stage being reviewed has to be part of the design review. coLigne AG plans formal design reviews at the [redacted]. Design review also is necessary if required in the [redacted] document. coLigne AG files the results of the design review, including identification of the design, the date, and the individuals performing the review in the design history file (DHF).

coLigne AG performs design verification, using existing documents [redacted] filed in the DHF and organized according to FDA and ISO requirements, to provide objective evidence that design output meets design input requirements. Your firm performs design validation using existing documents, including [redacted] to provide evidence that the design output conforms with user needs and intended use. Finally, your firm completes the [redacted] as part of the design plan to ensure that the device design is correctly transferred into production [redacted].

Please provide appropriate documentation showing that the design reviews have been planned and conducted at appropriate stages of the design process for the GII Spinal Fixation System.

2. Failure to establish and maintain design and development plans that define activities, responsibilities, and interfaces with different groups, as required by 21 CFR 820.30(b). Specifically, a design and development plan has not been established for the GII Spinal Fixation System.

Your firm's June 22, 2007, response letter appears to be inadequate. During the inspection, your firm's management was unable to provide the design and development planning for the GII Spinal Fixation System design project. Your firm's response indicates that coLigne AG has initiated an expanded and more detailed plan to control and verify the design of the product in order to ensure specified requirements are met per its design control requirements. This plan now describes, references, and documents the design and development activities required and defines responsibility for implementation. The new plan identifies and, describes the individuals and activities that provide, or result in, input to the design and development process. The plan is reviewed, updated, and approved as needed.

Please provide appropriate documentation showing that a design and development plan has been established for the GII Spinal Fixation System.

3. Failure to establish and maintain procedures to control changes to documents, as required by 21 CFR 820.40(b). Specifically, change control procedures were not established.

Your firm's June 22, 2007, response letter appears to be inadequate. During the inspection, your firm's management stated that there is no written change control procedure. Your firm's response indicates that procedures to fully develop change control associated with its products have been expanded. The new change control process now includes identification of the individual authorized to review and approve any design changes prior to implementation, and how the process is documented. This includes pre-production and post­production changes. Documentation will include the point at which control begins, the criteria used to accept change, and the procedures needed to define when verification and validation activities are needed.

Please provide appropriate documentation showing that the procedures for controlling changes to documents have been established.

4. Failure to adequately establish and maintain corrective and preventive action procedures that include the 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 product, or other quality problems, as required by 21 CFR 820.100(a)(1). Specifically, the corrective and preventive action procedures addressing the analysis of sources of quality data to identify existing and potential causes of nonconforming product or quality problems were not established.

Your firm's June 22, 2007, response letter appears to be inadequate. Your firm's response indicates that written procedures to control non-conforming product are under further review and development. The expanded nonconforming product procedures address all coLigne AG products, including its identification, documentation, evaluation, quarantine, and disposition. Any product that does not meet established specifications is evaluated to determine if a formal investigation is needed, and which individuals or activities must be notified.

Please provide revised corrective and preventive action procedures to address the above-stated requirements.

5. Failure to review, evaluate, and investigate any complaint involving the possible failure of a device, labeling, or packaging to meet any of its specifications, unless such investigation has already been performed for a similar complaint and another investigation is unnecessary, as required by 21 CFR 820.198(c). Specifically, no complaint investigation was conducted for the following undated complaints to find the root cause of the failure:

  • Complaint related to bent In Situ bender (customer complaint [redacted] and its IACAPA), which alleges that two pairs of bender instruments designed to bend the bar during surgery were bent themselves before they bent the bar. The corrective and preventive action (IACAPA) states "No Danger to Patient, but must be changed."

  • Complaint related a breakage of the instruments during a hook surgery (customer complaint [redacted] and its IACAPA), whose corrective measure section states "Exchange of instruments free of charge..." and "Design new hook holder..." The corrective and preventive action (IACAPA) states "Hook holder & starter Tip Broke, as in previous events. No harm to patient or Surgeon, but better solution must be designed. . . "

  • Complaint related to ostaPek plate that was broken during surgery (Product Ref/Description [redacted] complaint e-mail and its IACAPA)

Your firm's June 22, 2007, response letter appears to be inadequate. Your firm's response indicates that complaint handling has been reviewed, as well as new forms and procedures have been instituted to ensure that all complaints are uniformly evaluated, investigated, and reported as needed according to statutory requirements and deadlines.

Please provide appropriate documentation showing that a complaint investigation has been conducted for these complaints.

6. Failure to adequately establish and maintain procedures for receiving, reviewing, and evaluating complaints to ensure that all complaints are processed in a uniform and timely manner, as required by 21 CFR 820.198(a)(1). Specifically, the complaint handling procedures are inadequate in that they do not ensure all complaints are processed in a timely manner.

Your firm's June 22, 2007, response letter appears to be inadequate. Your firm's response indicates that complaint handling has been reviewed, as well as new forms and procedures have been instituted to ensure that all complaints are uniformly evaluated, investigated, and reported as needed according to statutory requirements and deadlines.

Please provide revised complaint handling procedures to ensure that all complaints are processed in a timely manner.

7. Failure of management with executive responsibility to appoint and document such appointment of, a member of management who, irrespective of other responsibilities, shall have established authority over and responsibility for the quality system requirements an d reporting, as required by 21 CFR 820.20(b)(3). Specifically, no management representative has been appointed to ensure that quality system requirements are met and to report to management on the performance of the quality system.

Your firm's June 22, 2007, response letter appears to be inadequate. Your firm's response indicates that a management representative is now designated to report to management on the performance of the quality system program and the extent to which the quality system meets its obligations.

Please provide appropriate documentation showing that this corrective action of appointing a management representative has been implemented.

8. Failure to adequately 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. Specifically,

a. The [redacted] quality audit schedule does not include the requirements of all the elements of the quality system, such as corrective and preventive actions, design control, records and document change control, etc.

b. The procedures for conducting quality audits [redacted] were not complete, in that they did not define the audit criteria, scope, methods, and frequency of the audit to be done, and no internal quality audit was performed in 2006.

Your firm's June 22, 2007, response letter appears to be inadequate. Your firm's response indicates that the quality system has been modified and updated to assure that design, production, and distribution of all coLigne product is now covered within the scope of its quality audit schedule. In addition, the procedures for conducting quality audits have been expanded to include the requirement of appropriate audit frequency for both the administrative and production sectors of the company. Production includes research and development areas. Frequency of audit is at [redacted] with the provision that additional audits may be required under defined circumstances including complaints and notified body or other regulatory authority requests.

Please provide the revised internal quality audit schedule to include all the elements of the quality system, as well as the revised quality audit procedures to address the audit, criteria, scope, methods, and frequency of the audit. Please also provide appropriate documentation showing that the corrective action of the quality audit performance has been implemented.

9. Failure to adequately establish and maintain procedures for acceptance of incoming product, as well as to failure to adequately document acceptance or rejection of the incoming product, as required by 21 CFR 820.80(b). Specifically, incoming product acceptance procedures and records did not show the equipment used in the tests and the results of certain acceptance activities.

Your firm's June 22, 2007, response letter appears to be inadequate. Your firm's response indicates that new procedures and forms are now in place to fully document equipment used, evaluation performed, and specific results obtained during the evaluation and inspection of all incoming products and materials used in the production of coLigne products and devices.

Please provide appropriate documentation showing that this corrective action of the incoming product acceptance procedures and records has been implemented.

In addition, please provide copies of your procedures and an explanation of how you ensure that all purchased or otherwise received product and services from your firm's contract [redacted] manufacturers confirm to specified requirements, as specified in 21 CFR 820.50.

You should take prompt action to correct the violations addressed in this letter. Failure to promptly correct these violations may result in regulatory action, which may include detaining your devices without physical examination upon entry into the United States until the corrections are completed under section 801(a) of the Act (21 U.S.C. § 381(a)). 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 violations, or similar violations, 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. If the documentation is not in English, please provide a translation to facilitate our review.

Your response should be sent to: Mr. William C. MacFarland, Chief of Orthopedic, Physical Medicine, and Anesthesiology Devices Branch, HFZ-343, Food and Drug Administration, Center for Devices and Radiological Health, Office of Compliance, Division of Enforcement B, 9200 Corporate Boulevard, Rockville, Maryland 20850. If you have any questions about the content of this letter, please contact: Mr. William C. MacFarland at telephone (240) 276-0293 or telefax (240) 276-0129.

Finally, you should know that this letter is not intended to be an all-inclusive list of the violations 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 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.

Sincerely yours,

/S/

Timothy A. Ulatowski
Director Office of Compliance
Center for Devices and
Radiological Health