Inspections, Compliance, Enforcement, and Criminal Investigations
Guilin Pharmaceutical Corporation, Limited 23-Jun-06
Department of Health and Human Services
Public Health Service
Rockville MD 20857
June 23, 2006
RETURN RECEIPT REQUESTED
In Reply refer to # CVM-06001 V
Mr. Xiaohua Yan
Guilin Pharmaceutical Corporation, Limited
No. 17 Shanghai Road
Guilin 541002 Guangxi, China
Dear Mr. Yan:
This letter is regarding the U.S. Food and Drug Administration (FDA) inspection of your Guilin Pharmaceutical Corporation manufacturing facility in Guangxi, China conducted from March 13 -16, 2006. A comprehensive current Good Manufacturing Practice (cGMP) inspection of your veterinary drug manufacturing was performed. As part of the inspection, a preapproval inspection for Abbreviated New Animal Drug Application [redacted] as conducted covering your active pharmaceutical ingredient (API) [redacted]. Additionally, Guilin Pharmaceutical Corporation manufactures the API's Levamisole Phosphate (for animal use) and Bumetanide (for human use) for the United States market.
The inspection of the veterinary drug manufacturing portion of the facility revealed significant deviations from cGMP. These observations indicate that these deficiencies are facility-wide problems. These cGMP deviations cause your firm's veterinary and human pharmaceutical products to be adulterated within the meaning of section 501(a)(2)(B) [21 U.S.C. 351 (a)(2)(B)] of the Federal Food, Drug, and Cosmetic Act (the Act) . Section 501(a)(2)(B) [21 U.S.C. 351 (a)(2)(B)] of the Act requires that the methods used in, or the facilities or controls used for, the manufacturing, processing, packing, and holding of drugs be in conformity with cGMP. No distinction is made between human and veterinary drugs and the failure of either to comply with cGMP constitutes a failure to comply with the requirements of the Act. FDA's Center for Drug Evaluation and Research (CDER), Office of Compliance, has also reviewed the inspection report and concurs with this decision as it applies to the manufacture of human drugs.
We acknowledge that your firm has made some changes and corrections in response to inspectional findings. However, we have found that while some individual cGMP deficiencies may have been corrected, your firm has failed to institute sufficient corrections to Quality Management, and Documentation and Records Systems to achieve cGMP compliance for an API facility.
Our concerns include, but are not limited to ; the following cGMP deficiency:
There is no assurance that GMP-related documents including, but not limited to, batch production records, in-process test records, and qualification reports are true and accurate.
We reviewed your firm's April 24, 2006, responses to the inspectional observations submitted by your United States agent, Chemwerth Incorporated, Woodbridge, Connecticut, which was signed by [redacted]. We found that the responses still lack sufficient detail, explanation, documentation, or substantive corrective action plans to adequately address the deviations noted during the March 2006 inspection of your manufacturing facility in Guangxi, China. For example, you stated that your firm thoroughly investigated the concerns that the FDA investigator raised during the inspection. One of FDA's major concerns continues to be that your firm has not adequately reviewed and reported whether the final batch production records, in- process test records, and qualification reports contain true and accurate information. The response lacks any information as to the authenticity of the values that appear on the final documents for the Levamisole lots documented on the FDA 483. You need to thoroughly investigate the discrepancies regarding these lots, as well as other batches of Levamisole and Bumetanide that may have been associated with these discrepancies.
Your response indicates that the firm revised the Batch Record ManagementlDocumentation Procedure and Raw Data Documentation Procedure, hired an additional person, and retrained employees on cGMP requirements. As part of the revised Batch Record Management procedure, the batch record will now be sequentially colored coded. We are unsure of what you meant by sequential color-coding or how this will ensure that records, including copies of records, are true and accurate. Additionally, the response does not address any corrections for the Qualification Reports.
Your response indicates that the Quality Assurance personnel, Quality Control personnel, and Operators from all the Workshops are receiving cGMP training. The response states that the training started on or about April 1, 2006, but you do not state when this training will be completed.
The cGMP deviation identified above is not to be considered an all-inclusive list of the deficiencies at your facility. FDA inspections are audits and are not intended to determine or disclose all problems or deviations that exist at a firm. We recommend that you continually evaluate your facility on an overall basis to determine cGMP compliance.
You should take prompt action to correct these violations. If corrections are not made, your firm's products may be placed on import alert and be denied entry into the United States. Articles can be refused admission pursuant to Section 801(a)(3) [21 U.S.C. 381(a)(3)] of the Act if the articles appear to be adulterated, including because the methods and controls used in their manufacture do not appear to conform to cGMP within the meaning of Section 501(a)(2)(B) [21 U.S.C. 351 (a)(2)(B)] of the Act.
Until FDA has confirmed cGMP compliance and that correction of the deficiencies noted above has been achieved, this office will recommend disapproval of any new applications listing your firm as the manufacturer of APIs. In addition to cGMP compliance issues, the pre-approval inspection identified additional information FDA would need for a complete evaluation of the manufacturing of [redacted]
Please notify this office in writing within 30 days of the specific steps you have taken to correct the noted violations, including an explanation of each step being taken to identify and make correction to any underlying systems problems necessary to assure that similar violations will not recur. Please include any and all documentation, in English, to show that adequate correction has been achieved. In case of future corrections, an estimated date of completion, and documentation showing plans for correction should be included with your response to this letter.
Please address your response and any questions to the Food and Drug Administration, Center for Veterinary Medicine, William Bargo, Compliance Officer, 7519 Standish Place, Room 103, Rockville, Maryland 20855. Remember to include your Firm Establishment Indicator number (3002807125) in all your correspondence.
Gloria J. Dunnavan
Division of Compliance (HFV-230)
Office of Surveillance and Compliance-
Center for Veterinary Medicine