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U.S. Department of Health and Human Services

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Enforcement Actions

Xylo Chem Industries 11/15/11

  

Department of Health and Human Services logoDepartment of Health and Human Services

Public Health Service
Food and Drug Administration
 Silver Spring  MD 20993 

 

Warning Letter
 
VIA UPS MAIL                                                                               WL: 320-12-003
 
November 15, 2011
 
Mr. Rajendra Patel, Managing Partner
Xylo Chem Industries
C-3/1, G.I.D.C. Estate
Nadiad 387001
Gujarat, India
 
Dear Mr. Patel:
 
During our July 11-16, 2001 inspection of your active pharmaceutical ingredient (API) manufacturing facility, Xylo Chem Industries located at C-3/1, G.I.D.C. Estate, Nadiad 387001, Gujarat, India, an investigator from the Food and Drug Administration (FDA) identified significant deviations from Current Good Manufacturing Practice (CGMP) for the manufacture of APIs. These deviations cause your API(s) 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, their manufacture, processing, packing, or holding do not conform to, or are not operated or administered in conformity with, CGMP.   
 
We have reviewed your firm’s response of July 31, 2011, and note that it lacks sufficient corrective actions.   
 
Specific deviations observed during the inspection include, but are not limited, to the following:
 
1.    Failure to have batch production records for each intermediate and API with  complete information regarding the production and control of each batch.
 
The “Manufacturing Report” batch documentation, provided by your firm during the FDA inspection, was incomplete. For example, specific instructions for each manufacturing step, the results of the process parameters monitored during production, deviations, and the results of release testing were not included.
 
In your response, you committed to revise the batch records and SOP, and have the revisions implemented by May 25, 2012.  Your response is inadequate because it failed to describe the control measures you will implement to ensure product quality while the process of updating the SOPs and batch records is ongoing. In addition, you failed to describe the specific instructions you intend to add to the batch records and which SOPs you will be updating.  Further, your written response indicated that there had been no need to change your manufacturing SOPs since 1999, but acknowledges that the batch records did not include the necessary information. Please explain why this deficient practice persisted for such an extended period in your quality system.
 
2.    Failure to have laboratory control records which include complete data derived from all tests conducted to ensure compliance with established specifications and standards.
 
The laboratory notebooks reviewed during the inspection were incomplete, including a lack of fundamental quality control data. Data missing and therefore not available for inspection included:  the raw data generated during testing, a record of all calculations performed in connection with the test, and a date and signature of a second person that demonstrates that the original records had been reviewed for accuracy, completeness, and compliance.
 
Your written response indicated that you are implementing a system to track analytical raw data for five years and that SOPs will be updated and implemented by May 25, 2012.  Please include a list of the specific SOPs and laboratory records that you plan to revise. Also include in your response a retrospective evaluation of all the raw data missing per product and lot produced, and make a determination of the impact a lack of such data may have on the quality of the product. Include information regarding the implementation dates and training program that will be developed as part of your corrective action plan.
 
3.    Failure to have an API expiry or retest date that is based on the evaluation of data derived from stability studies.
 
During the FDA inspection, your firm failed to provide the data to support the (b)(4) year retest date established for the (b)(4), USP API. The inspection found that your firm only has data to support a three year retest date. In your written response you indicated that you store samples for (b)(4) years but only test for stability “after 6 months, 1-year, and 3-year. [sic]” 
 
In your response to this letter please provide stability data to support your current (b)(4) year retest date and information to assure that your analytical method is stability indicating.
 
We also note that your July 31st, 2011 response indicates, in reference to the corrections being made, that they will be effective immediately.  However, your response also indicates that the SOP will be updated and validated by May 25, 2012. Please clarify this discrepancy.  Provide specific information regarding the timelines related to the implementation of your corrective actions.
 
In addition to the items listed above, the inspection uncovered other deficiencies that lead us to question the effectiveness of your current quality system to achieve overall compliance with CGMP at your facility.  An example of these deficiencies is the failure to provide documentation to demonstrate that the analytical methods used to test incoming raw materials, in-process samples, and finished products are adequate for their intended use. We recommend that you seek the advice of a third-party consultant for assistance with a complete evaluation to determine the improvements that will be needed at your firm to meet the CGMP requirements for the manufacture of APIs.
 
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 APIs 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. 
 
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 an API manufacturer. In addition, failure to correct these deviations may result in FDA refusing admission into the United States of articles manufactured at Xylo Chem Industries located at C-3/1, G.I.D.C. Estate, Nadiad 387001, Gujarat, India. The articles are subject to refusal of admission pursuant to section 801(a)(3) of the Act [21 U.S.C. § 381(a)(3)] because 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. Please identify your response with FEI # 3003747592.
 
If you have questions or concerns regarding this letter, contact Douglas A. Campbell, 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, Room 4240
10903 New Hampshire Ave
Silver Spring, MD 20993
Tel:    (301) 796-3201
Fax:    (301) 847-8741
 
 
Sincerely,
/S/ 
Steven Lynn                                                                 
Director
Office of Manufacturing and Product Quality
Office of Compliance
Center for Drug Evaluation and Research