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U.S. Department of Health and Human Services

Inspections, Compliance, Enforcement, and Criminal Investigations

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Arkray Factory, Inc. 6/15/09


Department of Health and Human Services' logoDepartment of Health and Human Services

Public Health Service
Food and Drug Administration
  2098 Gaither Road
Rockville MD 20850



Arkray Inc.
clo Mr. Shigeru Doi
President and CEO
Kyoto Miyuki Building 10F
689 Takanna-Cho
Kyoto 604-8153

Dear Mr. Doi:
During an inspection of your firm located in Ritto-Shi, Shiga-ken, Japan on February 10, 2009 through February 13,2009, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures Glucose Test Systems. 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 manufacture, packing, storage, or installation are not in conformity with the Current Good Manufacturing Practice (CGMP) requirements of the Quality System (QS) regulation found at Title 21, Code of Federal Regulations (C.F.R.), Part 820. We received responses dated March 3,2009 and April 15, 2009, from Mr.Seigi Nonofaki, CEO & President, concerning our investigator's observations noted on the Form FDA 483, List of Inspectional Observations that was issued to you. We address these responses below, in relation to each of the noted violations. These violations include, but are not limited to, the following:

1. Failure to establish and maintain adequate procedures and records for the review and disposition of non-conforming product to include retesting and reevaluation, and where appropriate, investigation as required by 21 CFR 820.90. For example:

a) Your firm did not follow its (b)(4) in that when a non-conformity occurred and it was deemed to be "OK", the individual authorizing the use of the product, did not document the action by signing off on the action. Additionally, the non-conformance slip was discarded after the evaluation. For non-conforming product that was deemed not to be "OK", the firm's SOP requires that the product be returned to the Parts Control Team or the Production Technology Team for a Cause Investigation. Your firm failed to follow the SOP and discarded the non-conforming products along with the non-conformance slips.
b) According to the firm's (b)(4), no rework activity is allowed at this facility, only retest/or recheck of the X-meters. However, the nonconforming procedure does not delineate when an investigation into these nonconformances should occur and how that
evaluation and investigation should be documented.

Your responses dated March 3, 2009, and April 15, 2009, are not adequate. The nonconformance procedure does not appear to address when investigations will be required and recorded. Your firm has taken corrective actions that include training of the factory manager, management staff, and production staff in the requirement to keep and maintain non-conformance records including copies of "non-conformance slips" and the disposition decision with the name and signature of the person authorizing the disposition. Your firm's corrective actions included the development of appropriate rework procedures, updating the (b)(4) and the training of facility staff in rework handling. Completed corrective actions are promised by August 16, 2009 with horizontal development completed and confirmation of corrective actions by January 31, 2010.

2. Failure to establish and maintain adequate procedures for receiving, reviewing, and evaluating complaints; and to ensure that complaints are evaluated to determine if complaints should be reported to FDA under Part 803 as required by 21 CFR 820.l98(a).
For example:

a) Your firm did not follow its own procedures (b)(4) and (b)(4) to evaluate the complaints for each of the MDRs received from Bayer. Your firm received (b)(4) MDR reports for 2007 and (b)(4) MDRs for 2008. However, none of the MDRs were considered to be complaints and were not processed as such.

b) The firm's complaint handling procedure, (b)(4), disclosed that the procedure does not require complaints to be evaluated for MDR reporting.

Your responses dated March 3, 2009 and April 15,2009, are not adequate. Your firm has assigned a working group to establish complaint handling procedures including the processing of MDR information. All MDR reportable events have been entered into the firm's computerized complaint handling system. The AFC (b)(4) has been updated to include additional details for processing MDRs and to include additional details for evaluating complaints for MDRs. AFC has conducted training in their updated complaint handling procedure. However, corrective actions will not be completed until July 28, 2009. Your firm planned to review the Corrective Action Plan at its Management Review meeting on April 18, 2009.

3. Failure to establish and maintain adequate procedures for corrective and preventive action (CAPA) to include the analysis of all data sources to identify existing and potential causes of nonconforming product as required by 820.100(a). For example:

a) Your firm's CAPA procedure does not include a requirement for data analysis. The only data analysis is performed by Bayer Healthcare, LLC and ARKRAY Factory USA, its sister company. No data analysis is performed by ARKRAY (Kusatsu) for MDRs and Non-Conformance Reports.

b) Your firm's CAPA procedure requires that the Corrective Action Report be completed within (b)(4) for (b)(4) and (b)(4) be completed with (b)(4) after issuance of a CAPA request. A review of (b)(4) CAPAs issued in (b)(4), revealed that (b)(4) Product CAPAs and (b)(4) System CAPAs were still open at the time of the inspection.

Your responses dated March 3, 2009 and April 15, 2009, are not adequate. AFC has developed a flowchart and related procedure (b)(4) to help educate staff and management about the requirements and benefits of quality data collection and analysis. AFC has analyzed MDR data on the Elite blood glucose system to examine the cause for MDR reportable events. Your firm has also collected and analyzed of (b)(4) X-Meter nonconformances. However, there are many other sources of quality data that the firm's responses do not address. Further, evidence of implementation has not been submitted. In addition, two of the six open CAPAs had been closed in 2008, but had been placed in external audit files that were not shown to the FDA investigator. Those two CAPAs were properly closed on February 25, 2009. AFC has committed to improve and modify its CAPA procedures. All relevant staff will be trained in the modified CAPA procedure. The modified CAPA procedure and evidence of implementation to include a retrospective review has not been submitted. Your firm planned to review the Corrective Action Plan at its Management Review meeting on April 18,2009.

You should take prompt action to correct the violations addressed in this letter for which you have not already provided an adequate response. 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 money penalties. Also, federal agencies are advised of the issuance of all warning letters about 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 deviations are reasonably related will not be approved until the violations have been corrected.

Please notify this office in writing within thirty (30) 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 violation(s), or similar violation(s), from occurring again. Include documentation of the corrective action 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 30 working days, state the reason for the delay and the time within which the corrections will be completed. Please provide a translation of documentation not in English to facilitate our review.

Your response should be sent to: James Woods (HFZ-440), 2098 Gaither Road, Rockville, MD 20850. If you have any questions about the content of this letter please contact Robert Fish at 240-276-0381 (telephone) or 240-276-0644 (fax).

This letter is not intended to be an all-inclusive list of the violation(s) at your facility. It is your responsibility to ensure compliance with applicable laws and regulations administered by FDA. The specific violation(s) noted in this letter and in the Inspectional Observations, Form FDA 483 (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 violation(s), and take prompt actions to correct the violation(s) and to bring your products into compliance.

A follow up inspection will be required to assure that corrections are adequate. We will contact the appropriate people and request an establishment re-inspection. An FDA trip planner will be in touch with you to arrange a mutually convenient date for this inspection.

Sincerely yours,



Donald St. Pierre
Acting Office Director
Office of In Vitro Diagnostic Device
Evaluation and Safety
Center for Devices and Radiological Health