Inspections, Compliance, Enforcement, and Criminal Investigations
Guangdong Baihe Medical Technology Co., Ltd 6/27/12
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
10903 New Hampshire Avenue
JUN 27 2012
VIA UNITED PARCEL SERVICE
Mr. Kai Huang
Guangdong Baihe Medical Technology Co., Ltd.
No. 89, Taoyuan East Road
Guangdong Province, P.R. China 528225
Dear Mr. Huang:
During an inspection of your firm located in Foshan, Guangdong Province, P.R. China, on March 26, 2012, through March 30, 2012, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures hemodialysis and central venous catheters. 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 responses from Ming Li, Deputy General Manager, dated April 17, 2012, and May 4, 2012, concerning our investigator's observations noted on the Form FDA 483 (FDA 483), List of lnspectional Observations, that was issued to your firm. We address the responses below, in relation to each of the noted violations. These violations include, but are not limited to, the following:
1. Failure to establish and maintain adequate procedures for monitoring and control of process parameters for validated processes to ensure that the specified requirements continue to be met, as required by 21 CFR 820.75(b).
For example, as part of the validation of the (b)(4) sterilization method, your firm evaluated the bioburden load of the devices prior to sterilization. The evaluation results were documented in the bioburden testing reports for the (b)(4) (Q52-01B02). However, your firm could not provide evidence that verified positive and negative controls were used during the evaluation of the bioburden load.
No results for positive or negative controls were documented in the bioburden testing reports. Your firm stated that positive and negative controls were not used for each incubation sample.
We reviewed your firm's responses and conclude that they are not adequate. Your firm revised the Bioburden Testing Standard Operating Procedure (SOP) to include the appropriate control methods, including positive and negative control. Your firm performed bioburden tests on three consecutive lots of products. However, your firm did not provide a plan and evidence of implementation of a systemic corrective action, including a review of other validation processes to ensure that adequate controls were used. Also, your firm did not provide any justification or statistical rationale for performing the bioburden tests on only three consecutive lots of product.
2. Failure to adequately ensure, 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, during the inspection, your firm stated that the microbiological part of the bioburden testing is conducted in accordance with the "Standard Methods of Microbiological Examination for Cosmetics Standard Plate Count" GB7918.2-87. This standard states that plates should be incubated at (b)(4). However, the bioburden testing reports for the (b)(4) indicated that the sample plates were incubated at (b)(4). Also, your firm could not provide documentation to verify that the sample plates were incubated (b)(4).
We reviewed your firm's responses and conclude that they are not adequate. Your firm revised its Bioburden Testing SOP to now stipulate that the standard "Microbiological Limit Test in Chinese Pharmacopeia and "GB/T19973.1-2005 Sterilization of Medical Devices - Microbiological Methods- Part 1, Estimation of Population of Microorganisms on Products" will be followed. Your firm performed bioburden testing on three consecutive lots of products using the revised SOP. However, your firm did not provide a plan and evidence of implementation of a systemic corrective action, including a review of other procedures using standards to ensure that the standards are properly being followed. Also, your firm did not provide any justification or statistical rationale for performing the bioburden tests on only three consecutive lots of product.
3. Failure to establish and maintain adequate procedures for acceptance of incoming product. Incoming product shall be inspected, tested, or otherwise verified as conforming to specified requirements. Acceptance or rejection shall be documented, as required by 21 CFR 820.80(b). For example, your firm's (b)(4), IQC004, requires that the (b)(4) be evaluated upon receipt. It further specifies that the weight of the product should be (b)(4). However, incoming inspection records for (b)(4) shipments 081230 (dated 2009-01-05) and 090602 (dated 2009-06-04) did not include evidence to indicate that the weight of the (b)(4) was evaluated.
Your firm's response to this observation appears to be adequate.
4. Failure to adequately document acceptance activities required by 21 CFR 820, as required by 21 CFR 820.80(e). For example:
A. For the (b)(4) testing performed on catheter lots after sterilization, Section 5, Annex D, of your firm's procedure, General Final Product Testing (052-04.5), states that (b)(4) However, upon request, your firm could not provide documentation to verify (b)(4) testing.
We reviewed your firm's responses and conclude that they are not adequate. Your firm revised Annex D (LAL Testing Procedure) of Q52-04.5 and the LAL Testing Record form to include requirements for the recording of the (b)(4). Your firm performed LAL testing and the records indicated that the (b)(4) time in/out and date were recorded. However, your firm did not indicate that it reviewed other testing procedures to ensure requirements for recording similar information (e.g., (b)(4)) were included in the procedure. Your firm also did not indicate that it reviewed historical testing reports to ensure that the necessary testing data were recorded. Lastly, your firm stated that the LAL tests performed demonstrated that all products subject to the previous established sterilization process complied with the requirements. However, no objective evidence was provided to support this statement.
B. The Sampling Plan in Table 9 of your firm's procedure, Standards for Physical Test (YZB 0001-2006), and the Configuration section of Q52-04.5 stipulate the number of syringe samples that should be used during final product testing of the central venous catheter set. However, no information was included in the final product testing reports for lots T809323, TR70243, T90035, TR70137, TR90019, and T70137 to verify that the appropriate number of syringe samples were used during final product testing. Also, your firm stated that the number of devices was not recorded.
We reviewed your firm's responses and conclude that they are not adequate. Your firm revised Q52-04.5 and the finished testing record form to include requirements for recording the sample quantities for each test item. Your firm provided results of testing performed on three lots of product and the records provided indicated that the quantity of samples tested was recorded. However, your firm did not indicate that it reviewed other testing procedures to ensure that requirements for recording the quantity of each test item were included in the procedure. Your firm also did not indicate that it reviewed historical testing reports to ensure that the quantity of devices being tested and other necessary data were recorded. Also, your firm did not indicate that it performed a retrospective assessment of historical catheter final product testing records to ensure that the proper number of syringes were evaluated and met specification prior to release.
5. Failure to adequately control labeling and packaging operations to prevent labeling mix-ups, as required by 21 CFR 820.120(d).
For example, during the inspection, the room in which labels were stored and printed was found to be unlocked and accessible by unauthorized personnel. Also, the computer used to print labels was not secure.
Your firm's response to this observation appears to be adequate.
Given the serious nature of the violations of the Act, hemodialysis and central venous catheters 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 violation(s) described in this letter. We will notify you if your firm's response appears to be adequate. We may need to re-inspect your firm's facility to verify that the appropriate corrections and/or corrective actions have been made.
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 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# 314978 when replying. If you have any questions about the contents of this letter, please contact: Carl Fischer, Ph.D., 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 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