Inspections, Compliance, Enforcement, and Criminal Investigations
X Spine Systems, Inc. 15-Jul-08
Department of Health and Human Services
Public Health Service
Cincinnati District Office
July 15, 2008
VIA FEDERAL EXPRESS
Dr. David L. Kirschman
X Spine Systems, Inc.
425 Alexandersville Road
Miamisburg, OH 45459-4223
Dear Dr. Kirschman:
During an inspection of your firm located in Miamisburg, Ohio on April 7 through April 18, 2008, investigators from the United States Food and Drug Administration (FDA) determined that your firm is the specification developer and distributor of implantable spinal systems. 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 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 manufacturing, packing, storage, or installation are not in conformity with the Current Good Manufacturing Practice (CGMP) requirements of the Quality System regulation found at Title 21, Code of Federal Regulations (C.F.R.), Part 820. We received a response from Brian K. Ruble, Official Correspondent, dated May 23, 2008, concerning our investigators' Form FDA 483 Observations (Form 483) that was issued to you at the close of the inspection. At this time, we cannot fully evaluate the adequacy of your response because, according to your firm's response, you are still in the process of developing procedures for the numerous proposed corrective actions. However, in this letter, we have attempted to address your firm's response, in relation to each of the noted violations. These violations include, but are not limited to, the following:
1. Failure to identify all actions needed to correct and prevent the recurrence of nonconforming product and other quality problems, as required by 21 C.F.R. § 820.100(a)(3). For example:
The original package insert for the Spider Cervical Plating System, which was released on or about 2/23/2006, listed three methods of steam sterilization. None of these methods had been validated. In January of 2007, your firm attempted to validate only one of these methods, the vacuum cycle at [redacted]F for [redacted] minutes and this validation failed. The validation was repeated with an increased exposure cycle of, [redacted] minutes and passed. Your firm revised the package insert on 9/18/2007, but did not notify any customers that the sterilization cycles listed in the package inserts with the implant systems distributed prior to 9/18/2007 would not assure a sterility assurance level of [redacted]
Your response to this observation does not appear adequate. Although your response states that a "Field Advisory Notice" will be sent immediately to customer sites for those devices that have not been implanted to assure customers follow the current revision of the package insert detailing the revised sterilization method, it does not address how you will assure that the appropriate corrective and preventive action will be taken when a nonconformance is identified in the future.
2. Failure of your complaint handling procedures to ensure that all complaints are evaluated to determine whether the complaint should be filed as a Medical Device Report, as required by 21 C.F.R. § 820.198(a)(3).
Specifically, there is no documented MDR assessment for the five medical device complaints your firm has received since January of 2006.
Your response states that you are updating your customer complaint procedure and form, and are also reviewing all complaints received since January of 2006 to evaluate whether they are reportable under 21 C.F.R. Part 803. You state this activity was completed by June 15, 2008. Please provide a copy of your complaint assessments, and the revised complaint procedure and form.
3. Failure to record the dates and results of complaint investigations, as required by 21 C.F.R. § 820.198(e)(6).
Specifically, four of the six complaints received since January of 2006 did not have documented failure investigations, including the individual performing the investigation and the date it was performed.
Your response states that you are revising the complaint form and are reviewing all complaints for complete investigations. Your response states the investigations were completed by June 30, 2008. Please provide a copy of the results of your investigations.
4. Failure to establish quality requirements that must be met by suppliers; and failure to obtain an agreement with your suppliers of implantable devices and instruments which states they will notify your firm of any changes in the product as required by 21 C.F.R. § 820.50(a) and (b).
For example, your firm has not established quality requirements for your suppliers/manufacturers of implantable devices and instruments. Additionally, there are no written contracts or agreements with your suppliers that state they will notify your firm of any design or manufacturing changes that could impact your product.
Your response states that you sent agreements to Level 1 suppliers of implantable devices and/or instruments by June 30, 2008. You also state that the Supplier Approval procedure will be revised to include the quality requirements expected from suppliers and require supplier agreements. Additionally, questionnaires will be sent to all suppliers by July 15, 2008. Please provide a copy of a questionnaire, supplier agreement and the revised procedure when completed.
5. Failure to clearly define the type and extent of control to be exercised over suppliers, as required by 21 C.F.R. § 820.50(a)(2).
For example, your Supplier Approval Procedure & Process Map states you will perform ongoing monitoring of Level 1 suppliers. The procedure does not define the frequency and type of monitoring required for these suppliers.
Your response states that the Supplier Approval procedure will be revised to include the specific requirements for conducting on-site supplier audits and include continued supplier monitoring. The procedure will be revised by July 15, 2008. Additionally, you are developing a Quality Plan for evaluating and auditing suppliers, which was completed June 30, 2008. Please provide a copy of the Quality Plan when completed.
6. Failure to evaluate potential contractors, as required by 21 C.F.R. § 820.50(a)(1).
For example, you did not evaluate the company who conducted steam sterilization validation studies for the Spider Cervical Plating System and Capless Pedicle Screw System to ensure they could conduct the validation studies in accordance with the specified standard.
Your response states that the Supplier Approval procedure will be revised to include the specific requirements for contractors and consultants.
7. Failure to demonstrate that the design was developed in accordance with the design control requirements of the QS regulation, as required by 21 C.F.R. § 820.30(a).
For example, the following design controls were inadequate during the development of the design of the Spider Cervical Plating System:
• Failure to approve the design and development plan, as required by 21 C.F.R. § 820.30(b). A design plan for the Spider system was not approved until 11/20/2006, which was after the devices were already in distribution (2/23/2006).
• Failure to address sterilization requirements in the design inputs, as required by 21 C.F.R. § 820.30(c).
• Failure to identify design outputs that are essential for the proper functioning of the device, as required by 21 C.F.R. § 820.30(d). The specific steam sterilization methods needed to properly sterilize the Spider system were not identified.
• Failure to perform design reviews at appropriate stages of the development of the device's design, as required by 21 C.F.R. § 820.30(e). Your "Design and Development Plan" states that a formal design review will be conducted at the conclusion of design activities. These activities were not defined and reviews were not completed.
• Failure to ensure that devices conform to defined user/patient needs and intended uses during design validation, as required by 21 C.F.R. § 820.30(g). You distributed the medical devices on or about 2/23/2006 and did not conduct steam sterilization validation for the sterilization method listed in the device's package insert until 7/24/2007.
• Failure to implement procedures to ensure that the device design was correctly transferred into production, as required by 21 C.F.R. § 820.30(h). You did not develop or review the work instructions and quality specifications and procedures used by your contract manufacturer.
Your response states that you are reviewing the design plans, inputs, outputs, validation, and reviews for the Spider Cervical Plating System, and the design history file will be updated by July 30, 2008. Additionally, your Product Design procedure will be revised by July 30, 2008, and training will be completed by August 15, 2008. Please provide an update on this corrective action and supporting documentation.
8. Failure to establish procedures that address incomplete, ambiguous, or conflicting design input requirements, as required by 21 C.F.R. § 820.30(c).
For example, your firm's "Product Design Procedure Map" does not include a mechanism for addressing incomplete, ambiguous, or conflicting design input requirements.
Your response states that your Product Design procedure, which will be revised by July 30, 2008, will address the process for identifying incomplete, ambiguous, or conflicting design input requirements.
9. Failure to have complete procedures for verifying that design output meets design input, as required by 21 C.F.R. § 820.30(f).
For example, although the "Product Design Procedure Process Map" defines design verification as "inspections that occur during the course of assembly, manufacturing, and processing," the procedure does not address how your firm will demonstrate the design outputs meet the design inputs.
Your response states that your Product Design procedure, which will be revised by July 30, 2008, will include the process for reviewing the design outputs versus the design inputs to ensure they are met.
10. Failure to address risk analysis in your design procedure, as required by 21 C.F.R. § 820.30(g).
For example, the "Product Design Procedure Process Map" does not address when risk analysis should take place and how it is to be conducted.
Your response states that your Product Design procedure, which will be revised by July 30, 2008, will include the requirements for conducting the risk analysis as part of the design and development activities.
11. Failure to include the signature of the approving official(s), the approval date, and when the change became effective on change records, as required by 21 C.F.R. § 820.40(b).
For example, your firm did not record the changes and approval dates of the package insert for the Capless Pedicle Screw System for the first three revisions (N60000277 Rev. A - Rev. C).
Your response states that your Document Control procedure, which will be revised by August 1, 2008, will indicate the scope of documents to be processed through the documentation system and training will be completed by August 15, 2008.
12. Failure to include complete records of approval and release of device labeling, including date and signature of the examiner in the device history record (DHR), as required by 21 C.F.R. § 820.120(b).
For example, your firm does not document the review and approval of package inserts prior to releasing them for use.
Your response states that the quantity, part number and revision number of the labels and package insert is being entered on the DHR. Please provide a copy of a completed DHR. Additionally, the work instruction, which was revised by June 15, 2008, will ensure this information is recorded and labels are reconciled.
You should take prompt action to correct the violations addressed in this letter. Failure to promptly correct these violations may result in regulatory action being initiated by FDA without further notice. These actions include, but are not limited to, seizure, injunction, and/or civil money penalties. Also, 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, no premarket submission to which the Quality System regulation deficiencies are reasonably related will 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 as to 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 actions 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, please state the reason for the delay and the time within which the corrections will be completed.
Your written response should be sent to Ms. Gina Brackett, Compliance Officer, Food and Drug Administration, 6751 Steger Drive, Cincinnati, Ohio, 45237. If you have any questions concerning the contents of this letter you may contact Ms. Brackett at (513) 679-2700, ext. 167, or you may forward a facsimile to her at (513) 679-2773.
Finally, you should know that this letter is not intended to be an all-inclusive list of violations at your firm. 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, 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 to bring your products into compliance.
Virginia R. Connelly
Acting District Director