Inspections, Compliance, Enforcement, and Criminal Investigations
International Brachytherapy Inc 08-Jun-04
Department of Health and Human Services
Public Health Service
Atlanta District Office
VIA FEDERAL EXPRESS
June 8, 2004
Ruth Feicht, President
International Brachytherapy Inc
6000 Live Oak Parkway, Suite 107
Norcross, GA 30093
Dear Ms. Feicht:
During an inspection of your firm located at the above referenced address on January 27 through February 2, 2004, Investigator Christie B. Rice determined that your firm manufactures and distributes permanent interstitial radiation implants. These products are devices as defined by Section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act).
The above stated inspection revealed that these devices are adulterated within the meaning of Section 501(h) of the Act, in that the methods used in, or the facilities or controls used for, their manufacturing, packing, storage, or installation are not in conformance with the Current Good Manufacturing Practice (CGMP) requirements of the Quality System Regulations for medical devices, as specified in Title 21, Code of Federal Regulations (21 CFR), Part 820. At the close of the inspection, you were issued a Form FDA 483 which delineated a number of significant GMP inspectional observations, including, but not limited to, the following:
1. Failure to fully validate and approve a process whose results cannot be fully verified by subsequent inspection and test, as required by 21 CFR 820.75(a). Your firm failed to ensure that the sterilization process for the EZ-Pak™ Preloaded Needles was adequately validated and approved according to established procedures. You could not provide documentation to show that the sterilization validation for the EZ-Pak™Preloaded Needles was adequately performed. Although your firm stated that the sterilization validation was performed in accordance with [redacted] Sterilization of health care products Radiation Sterilization, Substantiation of [redacted] kGy as a sterilization dose for small or infrequent production batches. However, documentation provided during the inspection did not show that this standard was, in fact, followed. In addition, there was no determination of bioburden level or verification dose.
2. Failure to implement procedures for monitoring and control of process parameters for validated processes, as required by 21 CFR 820.75(b). For example, your firm has failed to ensure that the sterilization process for the Z-Pak ™ Preloaded Needles is controlled and monitored. Quarterly dose audits for the [redacted] sterilization validation were not performed at designated intervals. The original radiation sterilization validation was performed in May 2001. Quarterly dose audits were performed in February 2002, May 2002, October 2002, and April 2003. No dose audits have been performed since April 2003. In addition, no documentation of quarterly dose audits were available for the EZ-Pak™ Preloaded Needles. Without initially identifying the bioburden levels of the EZ-Pak ™ Preloaded Needles, your firm is unable to determine whether changes have occurred in the bioburden level that may affect the sterilization dose.
3. Failure to appoint a management representative to ensure that the quality system requirements are met, and to report to management on the performance of the quality system, as required by 21 CFR 820.20(b)(3). Specifically, your firm has not appointed a management representative for this purpose, nor has it established a Quality Assurance department or designated personnel to oversee quality functions.
4. Failure to assure that quality audits are conducted by individuals who do not have direct responsibility for the matters being audited, as required by 21 CFR 820.22. For example, the person who conducts the quality audit for your firm is responsible for the very areas being audited.
5. Failure to inspect or test incoming product to verify conformance to specifications, as required by 21 CFR 820.80(b). For example, although your firm performs activity verification for all [redacted] seeds received no such verification activity is performed for the [redacted] devices received. Your firm has not provided adequate justification for not performing incoming inspection testing on the [redacted] devices received.
In addition, a review of our records reveals that there is no premarket notification (510(k)) clearance or premarket approval in effect for the EZ-Pak™ Preloaded Needle or Cartridge. The EZ-Pak™ Preloaded Needle and Cartridge requires a 510(k) because the modifications to the design or manufacturing process in which the seeds are delivered, as well as to the packaging of the [redacted] or [redacted] Iodine or Palladium seeds, are significant modifications that could substantially affect the safety of the device. Therefore, in accordance with 21 CFR 807.81(a)(3)(i), you must submit a new 510(k), addressing the new packaging, how the sterilization process is validated for the seeds and strands in the new configuration, and how the new configuration permits the user to perform his/her validation of seed activity-per good clinical practice.
The law requires that the manufacturer or the distributor of medical devices obtain marketing clearance for their products from FDA before they offer them for sale. This helps protect the public health by ensuring that new medical devices are shown to be safe and effective or substantially equivalent to other devices already legally marketed in this country. Because your devices do not have marketing clearance or approval from FDA, marketing, them in this country is a violation of the law. In legal terms, the products are adulterated under section 501(f)(1)(B) of the Act, for failure to obtain FDA premarket approval, and misbranded under section 502(o) of the Act, for failure to notify the agency of your intent to introduce the devices into commercial distribution. For a product requiring premarket approval before marketing, the notification required by section 510(k) of the act is deemed to be satisfied when a
premarket approval application (PMA) is pending before the agency. (21 CFR 807.81(b)).
This letter is not intended to be an all=inclusive list of deficiencies at your facility. It is your responsibility to ensure adherence to each requirement of the Act and regulations. The specific violations noted in this letter and in the FDA 483 issued at the close of the inspection may be symptomatic of serious underlying problems in your firm's manufacturing and quality assurance systems.
You are responsible for investigating and determining causes of the violations identified by the FDA. You also must promptly initiate permanent corrective and preventative action on your quality system. 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, FDA will not approve any applications for premarket approval (PMAs) for Class III devices to which the Quality System regulation deficiencies are reasonably related until the violations have been corrected. Also, no requests for Certificates For Export will be approved until the violations related to the subject devices have been corrected.
You should take prompt action to correct these violations. Failure to promptly correct these violations may result in regulatory action being initiated by the FDA without further notice. These actions include, but are not limited to, seizure, injunction, and or civil penalties.
Please provide this office in writing within fifteen (15) working days of receipt of this letter a report of the specific steps you have taken, or will take to identify and correct the noted violations, including an explanation of each step being taken to identify and make corrections to any underlying systems problems necessary to assure that similar violations will not recur. If corrective actions cannot be completed within fifteen (15) working days, state the reason for the delay and the time within which the corrections will be completed.
We acknowledge receipt of your letter dated February 10, 2004. We are currently reviewing your letter and will respond to it in a separate letter. You can refer to your February 10, 2004 response in your answer to this Warning Letter. Please send your response to the attention of Serene N. Ackall, Compliance Officer at the address noted in the letterhead. If you have any questions about this letter, you can contact Ms. Ackall at 404-253-1296.
Mary Woleske, Director