Inspections, Compliance, Enforcement, and Criminal Investigations

Asahi Kasai Medical Co., Ltd. 6/11/13


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

Public Health Service
Food and Drug Administration
 10903 New Hampshire Avenue
Silver Spring, MD 20993-0002 


June 11, 2013
Yutaka Shibata
Asahi Kasei Medical Co. Ltd.
2111-2 Oaza Sato
Oita Plant
Oita-shi, Japan
DearMr. Shibata:
During an inspection of your firm located in Oita-shi, Japanon March 11 through March 14, 2013, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures dialyzers, plasmapheresis and leukocyte reduction filters. 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.
Our inspection revealed that the your firm’s devices are misbranded under section 502(t)(2) of the Act, 21 U.S.C. § 352(t)(2), in that your firm failed or refused to furnish material or information respecting the device that is required by or under section 519 of the Act, 21 U.S.C. § 360i, and 21 CFR Part 803 - Medical Device Reporting.   We received a response from Yoshitada Itoh, General Manager, dated April 02, 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 report to FDA no later than 30 calendar days after the day that your firm received or otherwise became aware of information, from any source, that reasonably suggests that a device that your firm markets may have caused or contributed to a death or serious injury, as required by 21 CFR 803.50(a)(1). For example, your firm became aware of numerous events that were MDR reportable; however, your firm did not submit them to the agency within the 30 calendar day time period. Specifically,
A.    Your firm became aware of the event described in MDR 8010002-2013-00180 on 11/13/2008; the event described in MDR 8010002-2013-00200 on 5/27/2011; and the event described in MDR 8010002-2013-00230 on 1/24/2011.  These MDRs were not reported to FDA until 2/25/2013.
B.    Your firm became aware of the event described in MDR 8010002-2013-00250 on 8/3/2011; and the event described in MDR 8010002-2013-00040 on 9/15/2010. These MDRs were not reported to FDA until 3/1/2013.
C.    Your firm became aware of the event described in MDR 8010002-2013-00020 on 3/6/2012. This MDR was not reported to FDA until 2/26/2013.
The adequacy of your firm’s response cannot be determined at this time because it did not include a copy of the revised MDR procedure for review. We note that your firm conducted a retrospective review of complaints and submitted a total of (b)(4) MDR reports to the FDA, including the above MDRs.  
2.    Failure to adequately develop, maintain and implement written MDR procedures, as required by 21 CFR 803.17.  For example, your firm’s MDR procedure SOP-4TAQ-81001, Procedures for Safety Control Information Evaluation, Rev. 2.0 dated 11/19/2012, is deficient. Some examples of the deficiencies include:
A.    Your firm’s MDR procedure does not establish internal systems that provide for timely and effective identification, communication, and evaluation of events that may be subject to MDR requirements. Specifically, there are no definitions of what your firm considers to be a reportable event under 21 CFR Part 803. To facilitate the correct interpretation of reportable events and to assure the quality of MDR submissions, the MDR procedure should include definitions based on 21 CFR 803.3 for the terms “become aware,” “caused or contributed,” “malfunction,” “MDR reportable event,” and “serious injury,” and definitions for the terms “reasonably known” and “reasonably suggests,” found respectively in 21 CFR 803.50(b) and 803.20(c)(1).
B.    Your firm’s MDR procedure does not establish internal systems that provide for timely transmission of complete medical device reports. Specifically, the following are not addressed:
i.    Instructions for how to obtain and complete the FDA 3500A form.
ii.    The circumstances under which your firm must submit an initial, supplemental or follow-up report and the requirements for such reports.
iii.    The address for where to submit MDR reports: FDA, CDRH, Medical Device Reporting, P. O. Box 3002, Rockville, MD 20847-3002.
C.    Your firm’s MDR procedure does not describe how to address documentation and record-keeping requirements, including:
i.    Documentation of adverse event related information maintained as MDR event files.
ii.    Information that was evaluated to determine if an event was reportable.
iii.    Documentation of the deliberations and decision-making processes used to determine if a device-related death, serious injury, or malfunction was or was not reportable.
iv.    Systems that ensure access to information that facilitates timely follow-up and inspection by FDA.
If your firm wishes to submit MDR reports via electronic submission it can follow the directions stated at the following URL:
If your firm wishes to discuss MDR reportability criteria, it may contact the Reportability Review Team by email at:
In addition, FDA has noted nonconformances with regards to section 501(h) of the Act, 21 U.S.C. § 351(h), which are deficiencies within your firm’s quality system pertaining to current good manufacturing practice requirements specified in the Quality System regulation found at 21 CFR Part 820. These nonconformities include, but are not limited to, the following:
1.    Failure to establish and maintain adequate procedures for validating the device design. Design validation shall include risk analysis, where appropriate, as required by 21 CFR 820.30(g). For example, your firm implemented a new design involving (b)(4).  However, your firm’s risk analysis for these changes, dated 4/8/2005, failed to evaluate the risk of (b)(4).
We reviewed your firm’s response and conclude that it is not adequate.  Your firm conducted risk assessment and revised its Risk Assessment procedure to address the above deficiencies. However, your firm did not conduct a retrospective review of design history files for similar deficiencies. Additionally, your firm’s response did not provide a copy of the risk assessment report and revised Risk Assessment procedure for review.  

2.    Failure to adequately document Corrective and Preventive action activities and their results, as required by 21 CFR 820.100(b). For example, your firm’s nonconforming report #(b)(4) for (b)(4). However, your firm failed to document (b)(4) in the nonconformance report.  

The adequacy of your firm’s response cannot be determined at this time. Your firm revised its testing procedures, Test and Inspection Control Standard 3SAC-75000 and (b)(4) Manufacturing Control Standard 44SB-75001, to incorporate the requirements for proper testing and segregation of nonconforming devices. However, your firm’s response did not provide these procedures and personnel training records for review.  
3.    Failure to establish adequate procedures for management review, as required by 21 CFR 820.20(c). For example, your firm’s management review meeting, dated 4/4/2012, indicated that a (b)(4). However, the (b)(4) after the management review meeting.
The adequacy of your firm’s response cannot be determined at this time. Your firm revised its Management Control Standard procedure to include the requirements for implementing management review action items on time. However, your firm’s revised procedure and personnel training records were not provided for review.
A follow up inspection will be required to assure that corrections and/or corrective actions are adequate. 
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 action (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 to this letter 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 the Unique Identification Number (CMS case # 398405) when replying. If you have any questions about the contents of this letter, please contact: Debra Demeritt, Branch Chief, 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. 
Sincerely yours,
Steven D. Silverman
Office of Compliance
Center for Devices and
   Radiological Health
Yoshitada Itoh
General Manager
Regulatory Affairs Department
Asahi Kasei Medical Co., Ltd.
1-105 Kanda Jinbocho
Chiyoda-Ku, Tokyo 101-8101, Japan
Shinya Eguchi
US Agent
Asahi Kasei Medical America, Inc.
3570 Winchester Road, Suite 101
Memphis, Tennessee 38118

Page Last Updated: 04/09/2014
Note: If you need help accessing information in different file formats, see Instructions for Downloading Viewers and Players.
Language Assistance Available: Español | 繁體中文 | Tiếng Việt | 한국어 | Tagalog | Русский | العربية | Kreyòl Ayisyen | Français | Polski | Português | Italiano | Deutsch | 日本語 | فارسی | English