Inspections, Compliance, Enforcement, and Criminal Investigations
Arrowhead DE LLC, DBA Arrowhead Medical Device Technologies 5/18/12
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
New Orleans District
WARNING LETTER NO. 2012-NOL-21
UNITED PARCEL SERVICE
DELIVERY SIGNATURE REQUESTED
Patrick T. Mullaney, President
Arrowhead DE LLC, DBA
Arrowhead Medical Device Technologies
328 Poplar View Lane East, Suite 2
Collierville, Tennessee 38017
Dear Mr. Mullaney:
During an inspection of your firm, Arrowhead DE LLC, DBA Arrowhead Medical Device Technologies, located at 328 Poplar View Lane East, Collierville, Tennessee, on February 13-16 and 21, 2012, an investigator from the U.S. Food and Drug Administration (FDA) determined your firm manufactures orthopedic products for reconstructive surgery of toes and surgical instruments for the implantation of the orthopedic products. 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.
Our inspection revealed your devices 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 your response, dated February 28, 2012, concerning our investigator's observations noted on the February 21, 2012, FORM FDA 483, Inspectional Observations, (FDA 483) which was issued to you. Your responses are addressed below in relation to each violation. These violations include, but are not limited to, the following:
1. Failure to adequately validate with a high degree of assurance and approve according to established procedures, a process that cannot be fully verified by subsequent inspection and test required by 21 CFR 820.75(a). Specifically, your sole validation documentation addressing gamma sterilization of your products is included in a final report entitled "VD-Maxi (b)(4) Batch Release for 19mm Straight Implant" dated December 7, 2010. The Executive Summary section of this report states: "It should be noted that this dose has been validated for the batch tested; any additional batches of the same product would have to be validated separately." The Analysis section of this report states: (b)(4). In addition (b)(4). This study was conducted on (b)(4) units of 19mm straight implants (lot 10KSM0102; Catalog/Part 10-1019). In addition, data regarding the integrity of finished product packaging during sterile processing, storage, handling, and distribution was not available.
We reviewed your response and conclude it is not adequate. You state you have ordered further sterilization testing to complete the final sterilization validation activities; and, you enclosed a protocol entitled "VD max (b)(4) Gamma Radiation Validation for ARROW-LOK Fixation Device Implant Family," dated February 23, 2012. Furthermore, your long term corrective actions include addressing sterile packaging integrity after your final process sterilization validation activities have been completed and evaluated. Additionally, it is not clear whether you determined the cause for not having established validated procedures and processes.
2. Failure to establish and maintain procedures defining the responsibility for review and authority for disposition of nonconforming product, as required by 21 CFR 820.90(b)(1). Furthermore, disposition of nonconforming product shall be documented. Documentation shall include the justification for use of nonconforming product and the signature of the individual(s) authorizing the use. Specifically, on June 27, 2011, your contract sterilizer failed to include a dosimeter in the gamma sterilization process in which three lots of your Arrow-Lok Fixation Device (Lot V-2055 Straight 13mm; Lot V-2116 Straight 16mm; and, Lot V-2149 Angled 16mm) were processed. Your justification for the release and distribution of the three lots is dated February 16, 2012.
We reviewed your response and conclude it is not adequate as your corrective action remains in progress. You state in your response: "SOP 8.3.0 Control of Nonconforming Material will be re-written to include all requirements of 21 CFR Part 820.90 ... ".
3. Failure to establish and maintain procedures for implementing corrective and preventive action (CAPA), as required by 21 CFR 820.100(a). In particular, your procedure entitled "Corrective Action Preventive Action" (effective date February 7, 2012) does not include 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);
• Verifying or validating the CAPA to ensure that such action is effective and does not adversely affect the finished device, as required by 21 CFR 820.100(a)(4); and,
• Ensuring that information related to quality problems or nonconforming product is disseminated to those directly responsible for assuring the quality of such product or the prevention of such problems, as required by 21 CFR 820.100(a)(6).
The effectiveness of CAP A depends on the timeliness of implementing appropriate procedures. Documentation available for three CAPAs were initiated retrospectively on February 10, 2012; yet, the CAPAs are for incidents occurring sometime during or before December 2010 (CAPA 12-001), February 2011 (CAPA 12-002), and August 2011 (CAPA 12-003).
We reviewed your response, which includes a revised procedure, and it appears adequate; however, a follow up inspection would be required to assure corrective action has been adequate.
4. Failure to establish and maintain procedures to control the design of your Arrow-Lok Fixation Devices in order to ensure specified design requirements are met, as required by 21 CFR 820.30(a). Referring to your procedures entitled: "Design and Development" and "Engineering Change Notice" (both with effective date February 7, 2012) specifically:
• You failed to establish and maintain plans describing or referencing the design and development activities and defining responsibility for implementation; and, you failed to review, update, and approve plans as design and development evolved, as required by 21 CFR 820.30(b).
• You failed to establish and maintain procedures for verifying the device design to confirm the design output meets the design input requirements; and, you failed to document the results of design verification, including identification of the design, method(s), the date, and the individual(s) performing the verification, as required by 21 CFR 820.30(f).
• You failed to establish and maintain adequate procedures for validating the device design, including risk analysis where appropriate; and, you failed to maintain results of design validation, including identification of the design, method(s), the date, and the individual(s) performing the validation, as required by 21 CFR 820.30(g).
• You failed to establish and maintain adequate procedures to ensure the device design is correctly translated into production specifications, as required by 21 CFR 820.30(h).
• You failed to establish and maintain procedures for the identification, documentation, validation, or where appropriate, verification, review, and approval of design changes before their implementation, as required by 21 CFR 820.30(i).
Both of your design procedures ("Design and Development" and "Engineering Change Notice") have effective dates of February 7, 2012. Your Arrow-Lok Fixation Devices were distributed by December 2010. Documents, such as specifications, meeting notes, and product description were provided in retrospect as design development documentation. Changes made to your initial device design, including sterilization method (i.e. from (b)(4) to gamma sterilization), specifications (i.e. from Arrowhead Implant Specification Drawing 10-1010T Rev. (b)(4): to Arrowhead Implant Specification Drawing 10-1010T Rev.(b)(4), and secondary packaging (i.e. from (b)(4) to "flat pack" cardboard envelope), lacked change notices, change rationale, and evaluation as to whether the changes · would affect device function or quality.
We reviewed your response and conclude it is not adequate as your corrective action remains in progress. For example, you state: "Templates (forms) will be created for Design and Development and for Reporting on Design Verification and Design Validation."; your firm" ... will also revise SOP 7.3.0 Design and Development procedure to include all requirements for Design Transfer. ... "; your "SOP 7.4.1 Supplier Evaluation and Monitoring will be revised to include activities for establishing quality agreements .... "; and, "All previous product changes will be retrospectively documented through the newly approved and released SOP 4.2.5 Engineering Change Notice ..... "
5. Failure to establish and maintain procedures for acceptance activities, including inspections, tests, and other verification activities, as required by 21 CFR 820.80(a). Furthermore, per 21 CFR 820.80(d), finished devices shall not be released for distribution until: 1) the activities required in the device master record are completed; 2) the associated data and documentation are reviewed; 3) the release is authorized by the signature of a designated individual(s); and, 4) the authorization is dated. Specifically, your firm had no available receiving, in-process, or final acceptance activity documentation for your Arrow-Lok Fixation Devices (manufactured by a contract manufacturer and sterilized by a contract sterilizer) distributed before February 2012. All of your available data documenting final release activities for at least 27 lots of products were on your form entitled "QSF 26 Inspection Checklist Final Release" (effective date February 7, 2012) and dated either February 7 or 8, 2012.
We reviewed your response and conclude it is not adequate as your corrective action remains in progress. For example, you state: "QSF 26 Inspection Checklist will be revised to include actual final acceptance or rejection criteria from the contract sterilizer." Additionally, SOP 8.2.4 entitled "In-Process and Final Inspection and Final Product Release" (effective date February 20, 2012), does not reference 21 CFR 820.80.
6. Failure to adequately establish and maintain procedures for receiving, reviewing, and evaluating complaints by a formally designated unit, as required by 21 CFR 820.198. Specifically, your procedure entitled "Customer Complaints" (effective date February 7, 2012) does not ensure all complaints are evaluated to determine whether the complaint represents an event which is required to be reported to FDA under 21 CFR 803 -Medical Device Reporting, as required by 21 CFR 820.198(a)(3).
We reviewed your response and conclude it is not adequate as your corrective action remains in progress. For example, you state: "SOP 8.3.3 Customer Complaints will be revised to include missing requirements from 21 CFR Part 820.198."
Your firm 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, and civil money penalties. Federal agencies may be advised of the issuance of warning letters pertaining to devices so 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 violations 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) business days from the date you receive this letter of the specific steps your firm has taken to correct the noted violations, as well as an explanation of how your firm plans to prevent these violations, or similar violations, from recurring. Include documentation of the corrective actions (including any systemic corrective actions) your firm has taken. If your firm's planned corrective actions will occur over time, please include a timetable for implementation of those activities. If corrective actions cannot be completed within 15 business days, state the reason for the delay and the time within which these activities will be completed. Your firm's response should be comprehensive and address all violations included in this warning letter.
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.
Finally, you should know this letter is not intended to be an all-inclusive list of the violations at your firm's facility. It is your firm's 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 close of the inspection, may be symptomatic of serious problems in your firm's manufacturing and quality management systems. Your firm should investigate and determine the causes of the violations, and take prompt actions to correct the violations and bring the products into compliance.
Patricia K. Schafer
New Orleans District Office
Enclosure: FDA 483, dated February 21, 2012