Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
|10903 New Hampshire Avenue|
Silver Spring, MD 20993
September 5, 2013
VIA UNITED PARCEL SERVICE
Vincent Man Shing Choi
Vincent Medical (Don Guan)
Manufacturing Company, Limited
45-46 ShaBu Industrial Zone
Dong Guan City, Guang Dong
Dear Mr. Shing Choi:
During an inspection of your firm located in Dong Guan City, Guang Dong, China, on May 27, 2013, through May 30, 2013, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures breathing circuits and sterile fluid management injection 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 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. Your firm’s response dated July 10, 2013, to the Form FDA 483 (FDA 483), was not reviewed because it was not received within fifteen business days of issuance of the FDA 483. The response will be evaluated along with any other written material provided in response to the violations cited in this Warning Letter. These violations include, but are not limited to, the following:
1. Failure to establish and maintain procedures for implementing corrective and preventive action, as required by 21 CFR 820.100(a). For example:
a. Your firm’s “Corrective/Preventive Action” procedure, “MQSP8501, Revision G, Effective Date May 20, 2011,” is inadequate in that the procedure does not:
- Identify all sources of quality data that are to be analyzed to identify existing and potential causes of non conforming product, or other quality problems. The procedure is limited to (b)(4) for Investigation reports. There is no mention of (b)(4) associated with complaints, audits or any other quality data sources.
- Define the specific criteria required to initiate a corrective and preventive action (CAPA) investigation or when to implement corrective and preventive actions when (b)(4) have been identified.
- Define the specific requirements to verify or validate a corrective and preventive action to ensure that such action is effective and does not adversely affect the finished device. The procedure’s CAPA flowchart indicates that Verification of corrective/preventive action is required by QA; however, no further direction is provided.
- Include the requirement to ensure that CAPA activities are documented.
b. Complaint record NCIR-20130325-013 was initiated due to complaints of (b)(4) patient breathing circuit kits that were returned to (b)(4). Your firm indicated that the associated CAPA investigation included (b)(4) testing of the circuits; however, (b)(4) test results were not referenced in the complaint or CAPA record.
c. Complaint record NCIR-201304030-007 was initiated due to a report of a (b)(4) component on a pediatric breathing circuit. Your firm indicated that an investigation was completed in response to this report. A document, provided to (b)(4), titled, “The investigation report of (b)(4),” issued May 3, 2013, summarized your firm’s investigation. Your firm indicated that this issue was isolated to (b)(4) separate lots. Additionally, your firm indicated that the root cause of the malfunctioning (b)(4) was a (b)(4). However, your firm could not provide the documented results of the investigation, only the summary report that was sent to (b)(4).
d. CAPA investigations C1301281 and C1304221 were initiated for reports of (b)(4) breathing circuits reported in NCIR‑20130104‑014 and NCIR-20130419-015, respectively. In both situations, your firm could not provide complete documentation of the investigations, only reports that summarized investigational findings. Your firm indicated that effectiveness verification for CAPA C1301281 was the implementation and approval of the corrective actions by the customer. However, your firm did not verify or validate the corrective actions for effectiveness. Your firm’s Corrective/Preventive Action procedure, MQSP8501, effective Date May 20, 2011, requires “Verification of Corrective/preventive action,” to determine if the corrective/preventive action is satisfactory. However, your firm indicated that, for CAPA 1304221, the only effectiveness check performed was to verify that the corrective actions were implemented.
e. Complaint record NCIR-2012-02 was initiated due to complaints of “(b)(4).” An investigation was conducted for this complaint under CAPA C1202011. Your firm could not provide documentation of the effectiveness checks performed for this investigation to demonstrate that the corrective/preventive actions were satisfactory, as required under MQSP8501.
f. Your firm’s “Corrective/Preventive Action” procedure, MQSP8501, calls for issuance of a Quality Action Notice (QAN), as needed, for production nonconformities. However, there is no procedure or work instruction that defines how to issue, initiate, or complete a QAN. Additionally, your firm could not provide all of the QANs for products sold in the U.S.
2. Failure to ensure, when 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 procedure, as required by 21 CFR 820.75(a). For example:
a. CAPA C1202011 called for a validation of a new (b)(4) for an (b)(4) part identified in complaint record NCIR-2012-02. The protocol for the (b)(4) validation was documented in, “Validation Master Plan (b)(4),” Protocol Number, “(b)(4), Protocol Rev A.” Members from (b)(4), Engineering, and Quality Assurance departments signed and approved the validation protocol from February 20-22, 2012. However, during the review of the validation test reports for the new (b)(4), it was noted that both the Operation Qualification (OQ) and Process Qualification (PQ) reports were dated prior to the signed and approved protocol. The OQ was dated on February 18, 2012, and the PQ test report was dated on February 21, 2012.
b. Your firm could not produce any IQ records required under “Validation Master Plan, Protocol No.: (b)(4), Protocol Rev A,” for “(b)(4).”
3. Failure to establish and maintain procedures to ensure that participants at each design review include representatives of all functions concerned with the design stage being reviewed and an individual who does not have direct responsibility for the design stage being reviewed, as well as any specialists needed. The results of a design review, including identification of the design, the date, and the individuals performing the review, shall be documented in the design history file (DHF), as required by 21 CFR 820.30(e). For example:
a. Your firm’s previous and current “Product Design and Development Procedure, Document No.: MQSP7301, Revisions D and E,” effective dates: January 1, 2013, and May 14, 2013, respectively, do not include requirements to ensure that participants at each design review include representatives of all functions concerned with the design stage being reviewed and an individual who does not have direct responsibility for the design being reviewed.
b. Your firm’s “Product Design and Development Procedure, MQSP7301, Revision E, Effective Date: May 14, 2013,” did not include the requirement to ensure that the results of the design reviews are documented in the DHF. During a review of a (b)(4) design project, it was discovered that not all of the design review meeting minutes were kept in the DHFs. Your firm’s Quality Manual, “MQM 001, Revision W, Effective Date: May 23, 2013,” states that, “the DHF shall contain or reference the records necessary to demonstrate that the design was developed in accordance with the design plan and the and the requirements of this part.” Also, your firm’s “Product Design and Development Procedure” states that the Project Kick-Off meeting is the basis for the development plan. However, the Kick-Off meeting minutes were not kept in the DHF for the (b)(4) design project.
c. Your firm’s Design and Development Procedure does not specify which design review stages are required, nor does it define when the design review meetings should be held.
4. Failure to establish and maintain procedures to ensure that the device design is correctly translated into production specifications, as required by 21 CFR 820.30(h). For example, the design transfer section of your firm’s current and previous “Product Design and Development Procedure, MQSP7301, Revisions D and E,” effective dates: January 1, 2013, and May 14, 2013, respectively, requires mass production runs or “pilot runs” to “ensure the product can meet its intended use and are safe and effective.” MQSP7301 states that, during pilot runs, “Production should follow the normal mass production procedure to release and receive materials,” and “Quality Department should inspect ALL pilot run products and make records.” During a review of the DHF for the new (b)(4) project, your firm indicated that records were not kept for the release of pilot run products, the materials used, assembly operations performed, in-process test results, and inspection records. A (b)(4) Pilot Run Report, dated December 27, 2012, was provided by your firm; however, the report was just a summary of (b)(4). The only other documentation that your firm was able to provide was pilot run training records, the pilot run request, and the “Record of Customer Approval” form signed by the customer on January 30, 2013.
5. Failure to maintain complaint files and establish and maintain procedures for receiving, reviewing, and evaluating complaints by a formally designated unit, as required by 21 CFR 820.198(a). For example:
a. Complaint Record NCIR-20130325-013 was initiated due to reports of (b)(4) patient breathing circuit kits. The complaint was originally received via email on March 13, 2013, by the QA manager responsible for handling complaint investigations. However, the “Non Conforming Investigation Request” (NCIR) form, “MFOQA001,” which documents acceptance of a complaint, was dated March 25, 2013. Your firm’s “Handling of Customer Complaints Procedure, MQSP7202, Revision E, Effective Date: July 10, 2012,” requires that the marketing department fill out the NCIR form when an initial complaint is received. Additionally, the complaint investigation record did not include details of the reply to the complaint, even though a reply date of April 1, 2013, was noted on the NCIR form.
b. Complaint Record NCIR20130430-007 was initiated due to a report from (b)(4) that the (b)(4) on a pediatric breathing circuit was (b)(4). The complaint was originally received via email on April 22, 2013, by the QA manager responsible for handling complaint investigations. However, the NCIR form, “MFOQA001,” which documents acceptance of a complaint, was dated April 30, 2013. Your firm’s “Handling of Customer Complaints Procedure, MQSP7202, Revision E, Effective Date: July 10, 2012,” requires that the marketing department fill out the NCIR form, when a complaint is received. Additionally, your firm did not document a phone conversation made to (b)(4) in response to this complaint, as well as a complaint reply sent via email on May 3, 2013. A single reply date of May 7, 2013, was noted on the NCIR form.
c. Complaint record NCIR-20130104-014 was initiated on January 4, 2013, in response to reports of (b)(4) breathing circuits. However, your firm could not provide any documentation of the original complaint. Additionally, documentation of all complaint replies sent by your firm was not maintained. Your firm was able to provide email responses sent March 19-20, 2013. However, your firm could not provide documentation of a response on January 28, 2013, as noted on the NCIR form.
d. Complaint record NCIR-20130419-015 was initiated in response to reports of adult breathing circuit (b)(4). The QA manager indicated that your firm determined that the complaint was not a reportable event through a phone conversation with the complainant. However, the phone conversation was not documented in the complaint investigation record. Additionally, the NCIR form was initiated (b)(4) after receipt of the original emailed complaint. As stated above, your firm’s procedure, “MQSP7202,” requires the marketing department fill out the NCIR form when an initial complaint is received.
e. Complaint record NCIR-2012-02 was initiated in response to reports of “(b)(4).” The complainant, (b)(4), reported that this defect could be harmful to those handling the components. The original complaint was sent by email on December 2, 2011. However, the NCIR form was not initiated until (b)(4) later. According to your firm’s “Handling of Customer Complaints Procedure,” the marketing department is required to fill out the NCIR form when an initial complaint is received.
6. Failure to document acceptance activities required by this part, as required by 21 CFR 820.80(e). For example, the “(b)(4) inspection report, Doc. No. MFOAS103, Production Date: April 16, 2013,” did not have documented results for (b)(4). Additionally, the work instruction that covers this acceptance test, “MWI-51003224-AS-005, Revision C,” does not require documentation of the test results.
7. Failure to ensure that calibration procedures include specific directions and limits for accuracy and precision. When accuracy and precision limits are not met, there shall be provision for remedial action to reestablish the limits and to evaluate whether there was any adverse effect on the device’s quality, as required by 21 CFR 820.72(b). For example:
a. Your firm could not provide “review reports” to assess the impact on product when a temperature transmitter (sensor) was found to be out-of-calibration in the Ethylene Oxide (ETO) 10A Sterilizer. Sterilizer 10A had the associated equipment recalibrated for revalidation of ETO Sterilization process. (b)(4) Test Report, “TPR-006372, Rev: B, Completion Date: April 11, 2012,” indicated that (b)(4) temperature sensor had to be replaced with a new temperature sensor because, “The values given by this sensor were completely out of tolerance.” TPR‑006372 indicated that the new temperature sensor was checked with a calibrated oven and a certificate for successful calibration was issued. According to your firm’s procedure, “Control of Measuring/Test Equipment, Document No.: AQSP7601, Revisions F and G, Effective Dates: May 19, 2011, and April 10, 2013,” respectively, when equipment is found to be out of calibration, an assessment must be conducted to evaluate the impact to product or process. The assessment (review report) should then be recorded.
b. (b)(4) did not have any records of calibration. The (b)(4) is used to test for (b)(4) in manufactured devices. Your firm indicated that the (b)(4) had (b)(4) that required calibration. Section 6.2.2 of your firm’s “Calibration & Control of Measuring/Test Equipment, Document No: AQSP7601, Revision G, Effective date: April 10, 2013,” states that new equipment does not require calibration before first use if the calibration report from the manufacturer indicates that the equipment is qualified. The procedure further states that, if there is no calibration report, then the equipment has to be calibrated before first use. Your firm could not provide calibration records for (b)(4).
8. Failure to establish procedures for quality audits and conduct such 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. Corrective actions, including a reaudit of deficient matters, shall be taken when necessary, as required by 21 CFR 820.22. For example, your firm’s “Internal Audit and Control Procedure, Document Number, MQSP8202, Revision D, Effective Date: August 22, 2012,” does not define when reaudits are to be conducted.
9. Failure to control labeling and packaging operations to prevent labeling mixups. The label and labeling used for each production unit, lot or batch shall be documented in the device history record (DHR), as required by 21 CFR 820.120(d). For example, the primary identification labels of the individual devices were not included in the DHRs for Ballard Flex Circuit lots (b)(4) and (b)(4). The labels that were included in the DHRs for these lots were the labels for individual boxes containing (b)(4) of the units and labels for the boxes that contain (b)(4) packages of (b)(4) units.
Our inspection also revealed that 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. Significant violations include, but are not limited to, the following:
10. Failure to adequately develop, maintain and implement written MDR procedures, as required by 21 CFR 803.17. During the inspection of your firm, the MDR procedure titled “US Product MDR Event File and Recall Working Instruction,” MWIQA040 Revision B, 27 May 2013, was collected. The following issues were noted:
a. Your firm failed to implementMWIQA040 Revision B for documentation and recordkeeping requirements, including 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.
b. MWIQA040 Revision B does not establish internal systems that provide for timely and effective identification, communication, and evaluation of events that may be subject to MDR requirements. For example: there are no definitions of what your firm will consider 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 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)
c. MWIQA040 Revision B does not establish internal systems that provide for timely transmission of complete medical device reports. Specifically, the following is not addressed: MWIQA040 Revision Bdoes not include the address for where to submit MDR reports: FDA, CDRH, Medical Device Reporting, P. O. Box 3002, Rockville, MD 20847-3002.
The 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 #408035 when replying. If you have any questions about the contents of this letter, please contact: Carl Fischer, Ph.D., Chief, General Hospital Devices Branch at 301-796-5770 or by fax at 301-847-8137.
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