Inspections, Compliance, Enforcement, and Criminal Investigations
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
|Cincinnati District Office|
6751 Steger Drive
Cincinnati, OH 45237-3097
Telephone: (513) 679-2700
FAX: (513) 679·2771
November 30, 2010
Cynthia M. Brogan
1768 East 25th Street
Cleveland, OR 44114-4420
Dear Ms. Brogan:
During an inspection of your firm located in Cleveland, Ohio on October 13 through November 3, 2010, an investigator from the United States Food and Drug Administration (FDA) determined that your firm is manufacturing cranial plate implants. 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. These violations include, but are not limited to, the following:
1. Failure to establish and maintain procedures to control the design of the device in order to ensure that specified design requirements are met, 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 Cranial Plate Implant, which has been distributed since 2008:
a) Failure to establish a design and development plan, as required by 21 C.F.R. § 820.30(b).
b) Failure to establish design inputs, as required by 21 C.F.R. § 820.30(c).
c) Failure to implement your "Design Verification" procedure for verifying the device design, as required by 21 C.F.R. § 820.30(f). Specifically,
• Six of the eight design verification tests did not include a "Summation of the test outcome". Your procedure states a test report shall include the "Results of analysis compared to expected or predetermined outcome"; a "Summation and conclusion of the results compared to expected outcome"; and must be signed and dated by a designated individual.
d) Failure to validate the cranial implant design to ensure that devices conform to defined user/patient needs and intended uses, as required by 21 C.F.R. § 820.30(g).
2. Failure to establish procedures and to validate a process whose results can not be fully verified by subsequent inspection and test, as required by 21 C.F.R. § 820.75(a). Specifically,
a) The mixing, curing, casting, and cleaning processes used to manufacture the cranial plate implants have not been validated.
b) The implant's Instructions for Use states that "If re-sterilization is required the above instructions must be adhered to". Your sterilization validation did not include sterilizing the implant more than one cycle.
c) The implant's Instructions for Use states under the "Cleaning and Sterilization" section a sterilization parameter of "30-80% RH (relative humidity)". Your sterilization validation only included a 55% RH. The full range of 30-80% has not been validated.
3. Failure to establish corrective and preventive action procedures that include requirements for analyzing processes quality records and work operations to identify existing and potential causes of nonconforming product, or other quality problems, as required by 21 C.F.R. § 820.100(a)(1). For example,
Corrective and Preventive Action Procedure QSP4-02, dated 10/12/10 does not list manufacturing processes and nonconformances as data sources to be analyzed to identify existing and potential causes of nonconforming product, or other quality problems.
4. Failure to implement your procedures for the identification, documentation, validation or where appropriate verification, review and approval of all design changes before their implementation, as required by 21 C.F.R. § 820.30(i). Specifically,
Your "Engineering Change Notice Procedure No. QSP3-03" Rev C, dated 10/29/09, states in section 6.5 that "If a change does not require verification and/or validation, and associated risks are not affected, the reason is recorded on the ECN". All 11 ECN documents reviewed by the FDA investigator did not have the reason why no verification and/or validation were required completed on the form
5. Failure to maintain a device master record for the cranial plate implants, as required by 21 C.F.R. § 820.181.
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.
Teresa C. Thompson