Inspections, Compliance, Enforcement, and Criminal Investigations
Tianjin Hanaco Xingda Medical Co., Ltd. 12/5/12
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
|10903 New Hampshire Avenue|
Silver Spring, MD 20993
December 5, 2012
VIA UNITED PARCEL SERVICE
Tianjin Hanaco Xingda Medical Co., Ltd.
No. 4, Qijing Road
Dongli Economic Development Zone
Tianjin, China 300300
Dear Mr. Chen:
During an inspection of your firm located in Tianjin, China on August 13, 2012, through August 16, 2012, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures intravenous (IV) administration sets. 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 Peter Kuang, Vice General Manager, dated August 31, 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 acknowledge receipt of your firm’s five additional undated responses. They were not reviewed because they were not received within fifteen business days of issuance of the FDA 483. These responses will be evaluated along with any other written material provided in response to the violations cited in this Warning Letter.
We address the August 31, 2012 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 where 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 procedures, as required by 21 CFR 820.75(a). For example:
a) Your firm’s Process Validation Procedure (XD-3GUAN.JS-10, multiple versions) does not ensure that activities are adequately documented. During review of the (b)(4) validation for the J206 (b)(4) for a new IV administration set for a new customer, activities were not adequately documented. No IQ documentation identifying the (b)(4) machine used in the validation, no documentation of the OQ runs with parameter settings, and no documentation of equipment used in selected testing activities were available.
b) The (b)(4) Validation Protocol dated June 2, 2009, for a new single use IV administration set for a new customer did not adequately identify the drawing identification number/revision to be used to test and accept validation samples during IQ, OQ, and PQ runs.
c) Retesting of IV administration sets which (b)(4) testing with (b)(4) was not outlined or even mentioned in Work Instruction Product Name IV Administration Set (b)(4) Test dated March 24, 2010. This practice was not validated to address potential adverse effects by the (b)(4) used in the manufacture of the (b)(4).
The adequacy of your firm’s response cannot be determined at this time. Your firm indicated that it will revise the Process Validation Procedure, provide training, and check conformity of process validation documentation from 2010-2012 according to the revised procedure by September 30, 2012. Your firm also indicated that a retrospective validation of the (b)(4) will be conducted by October 15, 2012 and for all validation processes by March 15, 2013. However, without evidence of the completion of these activities, FDA cannot assess their adequacy.
2. Failure to establish and maintain adequate procedures to include requirements for implementing and recording changes in methods and procedures needed to correct and prevent identified quality problems, as required by 21 CFR 820.100(a)(5). For example, your firm’s CAPA Control Procedure (XD/CX 8.5.2/3, multiple versions) does not include requirements for addressing implementation of corrective and preventive actions and recording changes in your firm’s CAPA files. In addition, implementation of the corrective and preventive action was not recorded for (b)(4) of your firm’s CAPA files.
The adequacy of your firm’s response cannot be determined at this time. Your firm indicated that the CAPA Control Procedure will be revised, training will be provided, and all CAPAs from 2011-2012 will be retrospectively reviewed by September 30, 2012. However, without evidence of the completion of these activities, FDA cannot assess their adequacy.
3. Failure to adequately maintain a record of investigation, when an investigation is made under this section, by the formally designated unit identified in paragraph (a) of this section, as required by 21 CFR 820.198(e). For example, your firm’s Feedback Management Procedure (XD/CX 8.2.1, multiple versions) does not include requirements to ensure that records of investigations include the results of investigations. (b)(4) of your firm’s records of investigation into IV tubing damage did not include the investigation results of (b)(4) testing conducted as part of your firm’s investigation into the failure.
The adequacy of your firm’s response cannot be determined at this time. Your firm indicated that a third level document to supplement the missing elements of your firm’s Feedback Management Procedure will be drafted and training will be provided by September 15, 2012. Your firm also indicated that previous complaints will be retrospectively reviewed and effectiveness verification will be conducted by September 30, 2012. However, without evidence of the completion of these activities, FDA cannot assess their adequacy.
4. Failure to establish and maintain adequate procedures for finished device acceptance to ensure that each production run, lot, or batch of finished devices meets acceptance criteria, as required by 21 CFR 820.80(d). For example, the finished acceptance testing procedures for all standard (b)(4) do not include all criteria for (b)(4) testing. The requirement for testing (b)(4) was not documented in the procedure which was approved and in use since September 29, 2010.
The adequacy of your firm’s response cannot be determined at this time. Your firm indicated that it will revise finished acceptance criteria and provide training by September 10, 2012. Your firm also indicated that a retrospective evaluation of all finished device acceptance documentation and effectiveness verification will be conducted by October 31, 2012. However, without evidence of the completion of these activities, FDA cannot assess their adequacy.
5. Failure to use calibration standards for inspection, measuring, and test equipment that are traceable to national or international standards, or if national or international standards are not practical or available, to independently reproducible standards or established and maintained in-house standards, as required by 21 CFR 820.72(b)(1). For example, no calibration records traceable to national or international standards or an independent reproducible standard were available for instruments used for (b)(4) testing in the Quality Control lab.
The adequacy of your firm’s response cannot be determined at this time. Your firm indicated that it will draft a new procedure for calibrating (b)(4) test equipment to NIST traceable standards and (b)(4) test unexpired samples to ensure they met acceptance criteria by September 30, 2012. Your firm also indicated that effectiveness verification will be conducted by November 20, 2012. However, without evidence of the completion of these activities, FDA cannot assess their adequacy.
6. Failure to adequately document acceptance activities required by 21 CFR 820, as required by 21 CFR 820.80(e). For example, the equipment used in final acceptance testing was not identified in test results.
The adequacy of your firm’s response cannot be determined at this time. Your firm indicated that it will modify relevant inspection reports/records, provide training, and conduct effectiveness verification to ensure that traceability requirements are met by November 30, 2012. However, without evidence of the completion of these activities, FDA cannot assess their adequacy.
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 #365678 when replying. If you have any questions about the contents of this letter, please contact Carl Fischer, Ph.D., at 301-796-5770 or 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 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