Sysmex Corporation 22-Jan-02

DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

Food and Drug Administration

Center for Devices and Radiological Health

2098 Gaither Road

Rockville, MD 20850

JANUARY 22, 2002

WARNING LETTER

VIA FEDERAL EXPRESS

Mr. Hisashi Letsugu

President and CEO

Sysmex Corporation.

l-5-1 Wakinohama Kaigandori l-Chome

Chuo-Ku,

Kobe 651-0073,

Japan

Dear Mr. Letsugu:

During an inspection of your firm located in Hygo, Japan , on September 17-21, 2001, our investigator determined that your firm manufactures clinical laboratory diagnostic devices. Hematology, reticulocyte, urinalysis and coagulation analyzers are devices as defined by section 201(h) of the Federal Food, Drug and Cosmetic Act (the Act).

The above-stated inspection revealed that these devices are adulterated within the meaning of section 501(h) of the Act, in that the methods used in, or the facilities, or controls used for the manufacture, packaging, storage, or installation are not in conformance with the Current Good Manufacturing Practice (CGMP) requirements for medical devices which are set forth in the Quality System regulation, as specified in Title 21, Code of Federal Regulations (CFR), Part 820, as follows:

1. Failure to establish and maintain procedures for implementing corrective and preventive actions, as specified in 21 CFR 820.100. For example, there is no documented evidence of corrective actions taken when set limits have been exceeded.
2. Failure to ensure that information related to quality problems or nonconforming product is disseminated to those directly responsible for assuring the quality of such products or the prevention of such problems, as specified in 21 CFR 820.90. For example, you failed to establish procedures for monthly quality meetings at the Kakogawa factory.

3. Failure to establish and maintain procedures for validating the device design. Design validation shall be performed under defined operating conditions on initial production units, as specified in 21 CFR 820.3(g). For example, the procedure for the XE2100 did not define the operating conditions for the validation.

4. Failure to establish and maintain documented procedures to control and verify the design of the device in order to ensure that specified design requirements are met, as

specified in 21 CFR 820(a)(l). For example, there were no procedures for review of source codes in design controls for software validation, and there is no assurance that all lines and possibilities in the source codes are executed at least

once.

5. Failure to establish a system that ensures the prompt identification, timely investigation, reporting, documentation, and filing of device related death, serious

injury, and malfunction information, as specified in 21 CFR 820.100. For example, you have not established a Medical Device Reporting procedure. Of the 13 complaints reviewed, all of them lacked any evidence that they were evaluated in accordance with an MDR procedure.

This letter is not intended to be all-inclusive list of deficiencies at your facility. It is your responsibility to ensure adherence to each requirement of the Act and regulations.

The specific violations noted in this letter may be symptomatic of serious underlying problems your firm's manufacturing and quality assurance systems. You are responsible for investigating and determining the causes of the violations identified by the Food and Drug Administration. If the causes are determined to be systems problems, you must promptly initiate permanent corrective actions.

You should take prompt action to correct these deviations. Failure to promptly correct these deviations may result in regulatory acting being initiated by the Food and Drug

Administration without further notice. These actions include, but are not limited to placing your firm on import detention without physical examination.

We acknowledge that you have submitted a response dated November 6, 2001 concerning our investigator's observations noted in the form FDA 483. Your response will be verified at the next inspection of your facility.

Please notify this office in writing within fifteen (15) working days of receipt of this letter, of the specific steps you have taken to correct the noted violations, including an explanation of each step being taken to prevent the recurrence of similar violations. 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.

Any correspondence concerning this matter should be sent to Betty Collins, Chief, In Vitro Diagnostic Devices Branch or to Dr. A. Gonzalez-Licea, at 301-594-4595 ext.171 or by fax at 301-594-4636.

Sincerely yours,

Larry D. Spears

Acting Director

Office of Compliance

Center for Device and Radiological Health