Inspections, Compliance, Enforcement, and Criminal Investigations
Shandong Zibo Shanchuan Medical Instrument Co. Ltd. 1/13/12
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
10903 New Hampshire Avenue
JAN 13 2012
VIA UNITED PARCEL SERVICE
Chairman of the Board,
Shandong Zibo Shanchuan Medical Instrument Co. Ltd.
No. 88 Shancliuan Rd.
Zichuan District. Zibo City
Dear Mr. Xianliang:
During an inspection of your firm located in Zibo City, China, on October 24, 2011 , through October 27, 2011, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures sterile syringes. 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 in tended 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. These violations include, but are not limited to, the following:
1. Failure to adequately ensure that when the results of a process cannot be fully verified by subsequent inspection and test that the process is validated with a high degree of assurance and approved according to established procedures, as required by 21 CFR 820.75(a). For example:
• Your facility has (b)(4) chambers, of which (b)(4) are currently operational, for sterilization of syringe products. The annual sterilization process validation, conducted in 2011, was conducted only on chamber (b)(4) No validations were conducted on the remaining chambers.
• Your firm provided a performance qualification report for the sterilization process. This report indicates that the process flow for the sterilization cycle for the sterilization validation conducted in 2011 requires (b)(4) in a (b)(4) for (b)(4) The (b)(4) actual time was (b)(4) Furthermore, the (b)(4) was not yet operational at the time of the inspection.
• The annual sterilization validation protocol that your firm used for the sterilization validation conducted in 2011 requires the placement of (b)(4) and (b)(4) in each of the loads when performing the sterilization validation. Only (b)(4) and (b)(4) were placed in the load for the sterilization validation cycles run in 2011.
2. Failure to adequately establish and maintain procedures for implementing corrective and preventive action, as required by 21 CFR 820.100(a). For example, your CAPA No.s 1101 -01, 1102-01, 1103-01, 1107-01, and 1108-01 were all marked as effective, but there was no documentation to show that corrective and preventive actions had been implemented.
3. Failure 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). For example, your firm did not have procedures for design changes.
4. Failure to adequately establish and maintain procedures to ensure that equipment is routinely calibrated. inspected, checked, and maintained, as required by 21 CFR 820.72(a). For example: (b)(4)
5. Failure to adequately conduct quality audits to assure that the quality system is in compliance with the established quality system requirements and to determine the effectiveness of the quality system, as required by 21 CFR 820.22. For example, your firm's audit plan for 2011 includes requirements for auditing the production area for requirement numbers 8.2.3, 7.5.4, and 7.5.5. The audit of the production area, conducted on September 2011, did not include coverage of areas 8.2.3, 7.5.4 or 7.5.5, which were identified in the audit plan as being required.
6. Failure to adequately maintain procedures to ensure that device history records (DHRs) for each batch, lot, or unit are maintained to demonstrate that the device is manufactured in accordance with the device master record (DMR) and the requirements of this part, as required by 21 CFR 820.184. For example, the DHRs for your firm's Disposable 3-part Syringe do not include or refer to the location of documentation of the acceptance records which demonstrate that device is manufactured in accordance with the DMR and the primary identification label and labeling used for each production unit. Specifically, the DHRs for lot numbers 20110608 and 21000325 lack documentation of the labeling used on the devices and documentation to show that all of the records identified on the trace list were completed.
7. Failure to adequately maintain DMRs for each type of device which include or refer to the location of all the information required by 820.181, as required by 21 CFR 820.181(a). For example:
• The DMR (b)(4) which your firm uses to control the production of the Disposable 3-part Syringe, does not reference the 2 ml, 2.5 ml or 60 mL sizes.
• The procedure that your firm uses to control the quality control process is the (b)(4) procedure, SC/QS02387. However, the DMR references the following procedures for control of the quality control processes: (b)(4)
• The specifications for the (b)(4) operations lack specifications for the 2.0 ml, 2.5 mL, 30 ml, and 60 ml syringe sizes.
Our inspection also revealed that your Piston syringes are misbranded under section 502(t)(2) of the Act, 21 USC § 352 (t)(2), in that your firm failed or refused to furnish material or information respecting the devices that is required by or under section 519 of the Act, 21 USC § 360i, and 21 CFR Part 803- Medical Device Reporting (MDR) Regulation. Significant deviations include, but are not limited to:
Failure to adequately develop, maintain and implement written MDR procedures, as required by 21 CFR 803.17(a). For example, after reviewing your firm's MDR procedure entitled, (b)(4) File number SC/QP 10.0-01, Edition/time: A/0, effective date 2011/10/25, the following issues were noted:
1. SC/QP 10.0-01 does not establish a process that provides for the timely and effective identification, communication, and evaluation of events that may be subject to MDR requirements. For example:
• The definition of "MDR event" is not consistent with 21 CFR Part 803.3. To facilitate the correct interpretation of reportable events and to assure the quality of MDR submissions, your firm's procedure should include definitions based on 21 CFR Part 803.3 for the terms: "become aware," "caused or contributed," and "MDR reportable event," and definitions for the terms "reasonably known and reasonably suggests," found respectively in 21 CFR 803.50(b) and 803.20(c)(1).
2. SC/QP 10.0-01 does not establish a process that provides a standardized review or procedure to determine when an event meets the criteria for reporting under this part. For example:
• There are no instructions for conducting a complete investigation of each event and evaluating the cause of the event.
• The procedure, as written, does not specify who makes the decision for reporting events to FDA.
3. SC/QP 10.0-01 does not establish a process that provides for the timely submission of complete medical device reports. Specifically, the following are not addressed:
• Circumstances under which an event must be submitted as a 5-day report, and
• Circumstances under which your firm must submit initial, supplemental, or follow-up reports and the requirements for such reports.
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 or to schedule further communications, it may contact the MDR Policy Branch at 301-796-6670 or by email at MDRPolicy@fda.hhs.gov.
A follow up inspection will be required to assure that corrections and/or corrective actions are adequate.
Given the serious nature of the violations of the Act, the piston syringe, hypodermic needle and insulin syringes 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 you if your firm's response appears to be adequate.
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 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 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# 248314 when replying. If you have any questions about the contents of this letter, please contact: Dr. M. Isabel Tejera del Rio, General Hospital Devices Branch, at 1 (301) 796-5770 (phone) or 1 (301) 847-8137 (Fax).
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 lnspectional 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