| Public Health Service Food and Drug Administration |
Silver Spring MD 20993 |
Department of Health and Human Services
Warning Letter
VIA UPS MAIL
WL: 320-11-017
08/05/2011
Mr. Ruixin Miao
President/CEO
Nanjing Maohai Biotech Co.
8 Developing Zone
Yaxi Town, Gaochun County
Nanjing, Jiangsu Province
People’s Republic of China
Dear Mr. Miao:
During our October 25-28, 2010 inspection of your drug manufacturing facility, Nanjing Maohai Biotech Co. located at 8 Developing Zone, Yaxi Town, Gaochun County, Nanjing, Jiangsu Province, People's Republic of China, investigator(s) from the Food and Drug Administration (FDA) identified significant deviations from Current Good Manufacturing Practice (CGMP) for the manufacture of drugs. These deviations cause your (b)(4) to be adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (the Act) [21 U.S.C. § 351(a)(2)(B)] in that the methods used in, or the facilities or controls used for, its manufacture, processing, packing, or holding do not conform to, or are not operated or administered in conformity with, CGMP.
Specific deviations observed during the inspection include, but are not limited, to the following:
1. Failure of your quality unit to conduct review of completed batch production and laboratory control records before release for distribution.
For example,
Your firm lacks raw data to demonstrate that the ((b)(4)) test for the lots of (b)(4) shipped to the United States met the acceptance criteria. Your firm sends samples of (b)(4), produced by your firm, to your contract laboratory ((b)(4)) for (b)(4) testing. The material is released without adequate review of laboratory control records. Instead the results used for release are summary results accepted via text messaging, e-mail, or phone. In addition, your contract testing laboratory ((b)(4)) for proton-nuclear magnetic resonance (HNMR) only provides you with a partial spectra zoomed in on the range for ((b)(4)) and (b)(4). It is important for your firm to review the entire spectrum for other potential impurities or contaminants. All documents related to the testing of your (b)(4)should be reviewed and approved by your quality unit according to established procedures. Contract laboratories are an extension of your operations and, as such, your quality unit is responsible for all data acquired at the contract laboratories you choose to use.
2. Your quality unit fails to thoroughly investigate and resolve all quality-related complaints.
For example,
Complaints for four of (b)(4) lots of (b)(4) shipped to a customer (#(b)(4), # (b)(4) and #(b)(4)) were received and not properly documented or investigated by your firm. The customer rejected the lots for not meeting the customer’s specifications for the (b)(4) test. Your firm indicated that the (b)(4) had passed the (b)(4) test conducted by your contract testing laboratory. However, raw data pertaining to the test and retest performed by your contract laboratory was not available for your review and possible determination of a root cause.
The inspection also documented another complaint regarding an unknown impurity found in lot # (b)(4) of (b)(4) when tested using HNMR. No complaint investigation was conducted regarding this unknown peak.
Although this (b)(4) material did not ultimately reach U.S. patients, your firm has not demonstrated that it conducted a thorough investigation into the incident. Nor have you thoroughly investigated the potential contamination, identified the source of the potential contamination, or taken appropriate corrective actions to ensure the quality of the (b)(4) produced at your site.
Your firm’s failure to investigate these customer complaints is a serious deviation from CGMP. It is your responsibility to ensure that drugs manufactured at your facility are produced in compliance with CGMP. This includes establishing adequate systems to detect such quality issues before a product is distributed, and promptly implementing corrective measures to prevent recurrence.
3. Failure to have a system in place to evaluate suppliers, and failure to adequately test each batch of incoming materials intended to be used in drug production.
For example,
The inspection found that you have not evaluated the suppliers of (b)(4), (b)(4) and (b)(4), all used in the manufacturing process of (b)(4). Your firm currently accepts certificates of analysis (COA) from unevaluated suppliers in lieu of testing each batch of an incoming component to ensure conformity with the established specifications.
The deviations detailed in this letter are not intended to be an all-inclusive statement of deviations that exist at your facility. You are responsible for investigating and determining the causes of the deviations identified above and for preventing their recurrence and the occurrence of other deviations. If you wish to continue to ship (b)(4) to the United States, it is the responsibility of your firm to ensure compliance with all U.S. standards for CGMP and all applicable U.S. laws and regulations.
Additionally, your firm is neither registered nor has it listed every drug in commercial distribution in the United States with FDA, as required by 21 C.F.R. § 207.40 and section 510(i) of the Act [21 U.S.C. § 360(i)]. Information on how to register and list is available at the following internet website: http://www.fda.gov/cder/drls/registration_listing.htm. You must complete the required registration and listing and provide evidence that you have fulfilled these requirements in your response to this letter.
Until all corrections have been completed and FDA has confirmed corrections of the deviations and your firm’s compliance with CGMP, FDA may withhold approval of any new applications or supplements listing your firm as a drug manufacturer. In addition, failure to correct these deviations may result in FDA refusing admission of articles manufactured at Nanjing Maohai Biotech Co. located at 8 Developing Zone, Yaxi Town, Gaochun County, Nanjing, Jiangsu Province, People's Republic of China into the United States. The articles are subject to refusal of admission pursuant to section 801(a)(3) of the Act [21 U.S.C. § 381(a)(3)] in that the methods and controls used in their manufacture do not appear to conform to Current Good Manufacturing Practice within the meaning of section 501(a)(2)(B) of the Act [21 U.S.C. § 351(a)(2)(B)].
Within fifteen working days of receipt of this letter, please notify this office in writing of the specific steps that you have taken to correct deviations. Include an explanation of each step being taken to prevent the recurrence of deviations and copies of supporting documentation. If you cannot complete corrective action within fifteen working days, state the reason for the delay and the date by which you will have completed the correction. Additionally, your response should state if you no longer manufacture or distribute (b)(4), and provide the date(s) and reason(s) you ceased production. Please identify your response with FEI #3008548567.
If you have questions or concerns regarding this letter, contact Milva E. Meléndez, Compliance Officer, at the below address and telephone number.
U.S. Food and Drug Administration
Center for Drug Evaluation and Research
Office of Manufacturing and Product Quality
Division of International Drug Quality
White Oak, Building 51
10903 New Hampshire Ave
Silver Spring, MD 20993
Tel: (301) 796-0662
Fax: (301) 847-8741
Sincerely,
/Steven Lynn/
Steven Lynn
Director
Office of Manufacturing and Product Quality
Office of Compliance
Center for Drug Evaluation and Research
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