| Public Health Service Food and Drug Administration |
| New Orleans District 404 BNA Drive Building 200 – Suite 500 Nashville, TN 37217 Telephone: (615) 366-7801 FAX: (615) 366-7802 |
Department of Health and Human ServicesOctober 21, 2011
WARNING LETTER NO. 2012-NOL-01
UNITED PARCEL SERVICE
DELIVERY SIGNATURE REQUESTED
Daryl G. Newman, CEO
Cagenix, Incorporated
795 Ridge Lake Boulevard, Suite 107
Memphis, Tennessee 38120-9475
Dear Mr. Newman:
During an inspection of your firm, located at 795 Ridge Lake Boulevard, Suite 107, Memphis, Tennessee, on August 9-12 and 16, 2011, an investigator from the U. S. Food and Drug Administration (FDA) determined your firm is a manufacturer of Accuframe™ dental bridge frameworks. Under Section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act) [21 United States Code (USC) 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. You may find the specific regulations through links on FDA’s Internet home page at http://www.fda.gov.
This inspection revealed your Accuframe™ dental bridge frameworks are adulterated within the meaning of Section 501(h) of the Act [21 USC 351(h)] as the methods used in, or the facilities or controls used for, their manufacture, packing, storage, or installation do not conform with the Current Good Manufacturing Practice (CGMP) requirements of the Quality System (QS) regulation found at Title 21, Code of Federal Regulations, Part 820 (21 CFR 820). We received a response from you, dated September 2, 2011, concerning our investigator’s observations noted on the August 16, 2011, FORM FDA 483, Inspectional Observations, (FDA 483) issued to you. The responses are addressed below in relation to each violation. The 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 specified design requirements are met, as required by 21 CFR 820.30(a). For example, the following design controls were inadequate during the development of the design of the Accuframe™:
• Failure to establish and maintain plans describing or referencing the design and development activities and defining responsibility for implementation, as required by 21 CFR 820.30(b);
• Failure to establish and maintain procedures to ensure the design requirements are appropriate and address the intended use, including the needs of the user and patient, as required by 21 CFR 820.30(c);
• Failure to establish and maintain procedures, which contain or reference acceptance criteria and ensure design outputs, essential for the proper functioning of the device, are identified, as required by 21 CFR 820.30(d);
• Failure to establish and maintain procedures to ensure 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);
• Failure to establish and maintain procedures for validating the device design, as required by 21 CFR 820.30(g); and,
• Failure to establish and maintain procedures to ensure the device design is correctly translated into production specifications, as required by 21 CFR 820.30(h).
You state, corrective actions, relating to recently established design procedures, would have to be implemented during future development projects. Regarding the Accuframe™ devices, we understand your corrective action includes compiling historical data; however, you did not provide historical data in your response. Because of this, we cannot conclude whether this deficiency has been adequately addressed. We will verify the adequacy of any corrective action during a future inspection.
2. Failure to establish and maintain procedures for the identification, documentation, validation, or, when appropriate, verification, review, and approval of all design changes before their implementation, as required by 21 CFR 820.30(i). For example, during 2009, you changed the specifications for the titanium used to manufacture the Accuframe™ devices from ASTM (b)(4) to ASTM (b)(4). You did not document a rationale for the specification change or evaluate the effects, if any, of the design change. During 2009, at least ten Accuframe™ devices were manufactured using ASTM (b)(4) rather than ASTM (b)(4). Review of final acceptance activity documentation after November 9, 2009, revealed, during 2010 and 2011, either ASTM (b)(4) or ASTM (b)(4) were used to manufacture the Accuframe™ devices.
Your response states since both ASTM (b)(4) and ASTM (b)(4) are allowable for human implantation your firm did not provide scientific analysis or reporting on how the titanium under each standard compare. You further state this is a documentation deficiency only. Please note, after the initial design of a device is established, any change to your controlled design record requires the assessment of the change on your device, which may involve re-verification and re-validation. Design change is subject to document control and change control requirements. Your rationale for the change and assessment process as to whether the change affects device safety and effectiveness would be part of the design change documentation. You would also need to evaluate whether any changes to the design would require notification to FDA. Your response explains you have created a corrective action plan to assess the changes; however, you did not provide the corrective action plan. Because of this, we could not determine whether this deficiency has been adequately addressed. This will have to be evaluated during a future inspection.
3. Failure to establish and maintain procedures for changes to a specification, method, process, or procedure, as required by 21 CFR 820.70(b). Such changes shall be verified or, where appropriate, validated according to 21 CFR 820.75 before implementation and these activities shall be documented. Changes shall be approved in accordance with 21 CFR 820.40. For example, in-process inspection method and recording conditions required of your contract manufacturer was changed. You failed to provide documentation in regards to this change, such as, but not limited to: a rationale for the change; whether verification or validation would be required; or, whether this affected the original design protocol. Specifically, on an undocumented date, your contract manufacturer ceased measuring and recording the specification for the length of the area of articulation for the devices or “DPF” length during in-process inspection. During the inspection, your Operations Manager stated recording “DPF” length was not necessary because the same value was consistently held. However, examples provided below (See Number 4 below) indicate the “DPF” length has not been consistent.
Your response explains you created a corrective action plan to assess the changes; however, you failed to provide this plan with your response. Because of this, we could not determine whether this deficiency has been adequately addressed. This will have to be evaluated during a future inspection.
4. Failure to maintain adequate control of product that does not conform to specified requirements, including a determination of the need for an investigation and notification of the persons or organizations responsible for the nonconformance, as required by 21 CFR 820.90(a). For example:
• The Modeling form for Accuframe™ Lot 0148-001, released on July 15, 2011, documented a vector specification above the acceptable specification;
• The In Process Inspection form for Accuframe™ Lot 060-0039, released on March 15, 2011, documented a “DPF” Diameter specification greater than the allowable tolerance range;
• The In Process Inspection form for Accuframe™ Lot 09-00308, released on March 2, 2011, documented a “DPF” Length specification greater than the allowable tolerance range;
• The In Process Inspection form for Accuframe™ Lot 060-0035, released on February 16, 2011, documented a “DPF” Diameter specification greater than the allowable tolerance range;
• The In Process Inspection form for Accuframe™ Lot 09-00108, released on July 1, 2010, documented a “DPF” Diameter specification greater than the allowable tolerance range; and,
• The In Process Inspection form for Accuframe™ Lot RMAGALI098, released on June 1, 2010, documented a “DPF” Diameter specification greater than the allowable tolerance range.
The above lots were released without evidence of investigation of the issues or rationale for releasing the non-conforming products.
Your response explains you have created a corrective action plan to assess the changes; however, you failed to provide this plan with your response. Because of this, we could not determine whether this deficiency has been adequately addressed. This will have to be evaluated during a future inspection.
5. Failure to conduct complaint investigations when complaints involve the possible failure of a device to meet any of its specifications, as required by 21 CFR 820.198(c). For example:
• Customer Complaint Reports # 002 and 003, dated December 8, 2010, for Accuframe™ 081-001 and 081-002, document the nature of the complaints as “Bar Design Incorrect” and the assessment cause as “Method/Process…Design”. Follow-up by Technical Service Staff was marked as required. Specifics, such as the actual design aspect involved or what actually caused the device failure resulting in the complaint, were not documented.
• Customer Complaint Report # 004, dated February 16, 2011, for Accuframe™ 031-001, documents the nature of the complaint as “Distal Extension Broke. Review Design and…up where necessary & recut.” and the assessment cause as “Frame Design”. Follow-up by Technical Service Staff was marked as required. Specifics, such as the actual frame design aspect involved or what actually caused the device failure resulting in the complaint, were not documented. There is no documentation as to whether a patient was directly affected or not. There is no description of the complaint situation.
• Customer Complaint Report # 006, dated June 13, 2011, for Accuframe™ 059-001, documents the nature of the complaint as “Distal Extension Broke. Customer requested a recut of the same design.” and the assessment cause as “Method/Process…Design”. Follow-up by Technical Service Staff was marked as required. Specifics, such as the actual design aspect involved or what actually caused the device failure resulting in the complaint, were not documented. There is no documentation as to whether a patient was directly affected or not. There is no description of the complaint situation.
• Customer Complaint Report # 007, dated July 11, 2011, for Accuframe™ 07-0027, documents the nature of the complaint as “Right Distal Extension Broke.” and the assessment cause as “Method/Process…Design”. Follow-up by Technical Service Staff was marked as required. Specifics, such as the actual design aspect involved or what actually caused the device failure resulting in the complaint, were not documented. There is no documentation as to whether a patient was directly affected or not. There is no description of the complaint situation.
• Customer Complaint Report # 008, dated August 5, 2011, for Accuframe™ 0158-002, documents the nature of the complaint as “Customer complained of bar being too thin in area of DPF 3. Bar thickened and will be recut at no charge.” and the assessment cause as “Method/Process…Design”. Follow-up by Technical Service Staff was marked as required. Specifics, such as the actual design aspect involved or what actually caused the device failure resulting in the complaint, were not documented. There is no documentation as to whether a patient was directly affected or not. There is no description of the complaint situation.
Your response appears adequate; however, due to the nature of this observation, we will have to verify the adequacy of your corrective action during a future inspection.
6. Failure to establish and maintain procedures for implementing corrective and preventive action, as required by 21 CFR 820.100(a). Specifically, your written procedures do not address data collection, such as identifying what data will be collected and the frequency of data collection and analysis to identify existing and potential causes of nonconforming product, or other quality problems. Per 21 CFR 820.100(a)(1), you must use appropriate statistical methodology where necessary to detect recurring quality problems; and, 21 CFR 820.250 requires you to establish and maintain procedures for identifying valid statistical techniques.
Your response appears adequate; however, due to the nature of this observation, we will have to verify the adequacy of your corrective action during a future inspection.
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 the FDA without further notice. These actions include, but are not limited to, seizure, injunction, or civil money penalties. Federal agencies are advised of the issuance of all warning letters regarding devices so they may take this information into account when considering the award of contracts. Additionally, premarket applications for Class III devices 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.
This letter is not intended to be an all-inclusive list of 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 FDA 483, issued at the conclusion 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 action to correct the violations and to bring your products into compliance.
Please notify this office in writing within 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 recurring. Include documentation of any further 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, state the reason for the delay and the time within which the corrections will be completed.
Your response should be sent to: Rebecca A. Asente, Compliance Officer, at the address above. If you have any questions about the content of this letter, please contact: Ms. Asente at (504) 832-1290, extension 1104.
Sincerely,
/S/
Patricia K. Schafer
District Director
New Orleans District Office
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nice article. thank you.
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