Inspections, Compliance, Enforcement, and Criminal Investigations
Arriol International Corp. 7/20/12
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
|10903 New Hampshire Avenue|
Silver Spring, MD 20993
July 20, 2012
President & CEO
Arriol International Corp.
Carretera San Isidro Km. 17
Zona Franca San Isidro
Santo Domingo, Dominican Republic
Dear Mr. Armenteros:
During an inspection of your firm located in Santo Domingo, Dominican Republic, on April 09, 2012, through April 12, 2012, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures EZ IO intra osseous injection system and aseptic transfer kits for filling of breast 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 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 manufacture, packing, storage, or installation are not in conformity with the current good manufacturing practice requirements of the Quality System regulation found at Title 21, Code of Federal Regulations (CFR), Part 820.
We received a response from you dated April 27, 2012, concerning our investigator’s observations noted on the Form FDA 483 (FDA 483), List of Inspectional Observations, that was issued to your firm. We address this response below, in relation to each of the noted violations. These violations include, but are not limited to, the following:
1. Failure to adequately ensure that processes, work operations, concessions, quality audit reports, quality records, services records complaints, returned product, and other sources of quality data are analyzed to identify existing and potential causes of nonconforming product, or other quality problems, as required by 21 CFR 820.100(a)(1). For example, data from nonconforming product is not adequately analyzed and there is no mechanism to identify recurring nonconformances that may require corrective and preventive action.
Nonconforming data from each month is reviewed, but is not analyzed over a longer period of time to identify potential trends. Your firm has opened approximately (b)(4) nonconformances in 2012, but no investigations have been initiated in the last year in response to nonconformances.
We reviewed your firm’s response dated April 27, 2012, and conclude that is not adequate. Your firm stated that it has completed corrective action for Procedure Control of Non-Conforming Materials, Raw Materials, and Products (SDQ-115). Your firm provided a copy of procedure (SDQ-115) in its response; however, the procedure was not translated into English. Your firm also stated in its response that, on a monthly basis, unless there is a problem that requires immediate attention, your firm’s non-conforming materials will be evaluated and trended by your firm’s Materials Review Board, utilizing the Non-conforming Material Report and the Scrap reports issued by the Enterprise Resource Planning System. Your firm did not, however, include documentation or evidence of the corrections, corrective actions, or consideration of systemic corrective actions with its response, to include opening investigations for internally identified nonconformities.
2. Failure to adequately ensure, when the results of a process cannot be fully verified by subsequent inspection and test, that the process shall be validated with a high degree of assurance and approved according to established procedure, as required by 21 CFR 820.75(a). For example, your firm’s (b)(4) sterilization process validation, “Validacion De La Esterilizadora (IQ),” RVAE-10001-1, included (b)(4) testing on a full cycle sterilization for batches AV10C04-F03, AV9L07-FC03, and AV10C05 FC03, which were sterilized on April 21, 2010. However, your firm’s sterilized products were received and tested by the contract testing facility (b)(4) on May 05, 2010. Your firm’s validation (b)(4) testing did not establish actual levels of (b)(4) in sterilized products until (b)(4) after processing and did not demonstrate that the (b)(4) process would adequately remove (b)(4) from the product.
We reviewed your firm’s response dated April 27, 2012, and conclude that is not adequate. Your firm noted the sterilization validation protocol assumes that there is a minimum of (b)(4) before the product is released because all sterility and pyrogen testing results need to be available before the quality documentation is generated. Consequently, your firm started the (b)(4) testing after the (b)(4) quarantine period and states that it can demonstrate that the observed (b)(4) levels are below the maximum allowable limit after the quarantine period. In addition, your firm noted that it will construct an (b)(4) dissipation curve by obtaining (b)(4) levels during 20 days for all processed, terminally-sterilized products in order to determine the minimum hold time for your firm’s product. Your firm’s estimated completion date for these activities is June 2012. However, your firm did not provide documentation or evidence of the corrections. Also, your firm did not provide a plan and evidence of implementation of a systemic corrective action, including review of other validation processes.
3. Failure to adequately develop, conduct, control, and monitor production processes to ensure that a device conforms to its specifications, and failure to establish and maintain adequate process control procedures that describe any process controls necessary to ensure conformance to specifications, as required by 21 CFR 820.70(a). For example, your firm’s (b)(4) sterilization process procedure, “Procedimiento de Esterilizacion,” SDQ-080:
a. Describes the process parameters used to sterilize your product. However, there is not complete documentation of the monitoring of the (b)(4) process conditions during the sterilization cycle. There is no documentation of the actual process conditions, only a check mark verification that the specified requirements were met.
We reviewed your firm’s response dated April 27, 2012, and conclude that it is not adequate. Your firm opened CAPA #1204A002 in order to address the deficiency and to improve the current process controls. Your firm plans to upgrade the (b)(4) of an (b)(4) in order to electronically record all process data by December 2012. Also, your firm revised procedures “Product Release and Shipment of Finished Product,” SDQ-047, and “Sterilization Procedure,” SDQ-080, to mandate a (b)(4) minimum quarantine period for all sterilized products. However, your firm did not provide a plan and evidence of implementation of how the (b)(4) process will be controlled. In addition, your firm did not provide a plan of implementation of a systemic corrective action, including review of other process control procedures.
We note that your firm modified the Process Control Checklist, SDQ-080, to include the manual recording of all critical parameters at the time of completion of each phase of the sterilization cycle. A copy of the revised checklist was provided and appears to be adequate.
Given the serious nature of the violations of the Act, EZ-IO intra osseous injection system and aseptic transfer kits manufactured by your firm are subject to refusal of admission under section 801(a) of the Act, 21 U.S.C. § 381(a), in that they appear to be adulterated. As a result, FDA may take steps to refuse these products, known as "detention without physical examination," until these violations are corrected. In order to remove the devices from detention, your firm should provide a written response to this Warning Letter as described below and correct the violations described in this letter. We will notify your firm if its response appears to be adequate. We may need to re-inspect your firm’s facility to verify that the appropriate corrections and/or corrective actions have been made.
Also, U.S. federal agencies may be advised of the issuance of Warning Letters about devices so that 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 deviations 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 business days from the date you receive this letter of the specific steps your firm has taken to correct the noted violations, including an explanation of how your firm plans to prevent these violations, or similar violations, from occurring again. Include documentation of the corrections and/or corrective actions (including any systemic corrective actions) that your firm has taken. If your firm’s planned corrections and/or corrective actions will occur over time, please include a timetable for implementation of those activities. If corrections and/or corrective actions cannot be completed within fifteen business days, state the reason for the delay and the time within which these activities will be completed. Please provide a translation of documentation not in English to facilitate our review.
Your firm’s response should be sent to: Food and Drug Administration, Center for Devices and Radiological Health, Office of Compliance, Field Operations Branch, White Oak Building 66, Rm 2609, 10903 New Hampshire Ave., Silver Spring, MD 20993. Refer to CMS case #314339 when replying. If you have any questions about the contents of this letter, please contact: Carl Fischer at 301-796-5770.
Finally, you should know that 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 Inspectional Observations, 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.
Steven D. Silverman
Office of Compliance
Center for Devices and