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Released by FDA:  2/21/06.  Posted by FDA:  4/10/06

Mr. Raju Krishna Swamy
Vice President - Manufacturing
Wockhardt Ltd.
L-1, MIDC Area,
Chickalthana Aurangabad - 431 210
India

Dear Mr. Swamy:

We. have completed our review of the inspection of your pharmaceutical manufacturing facility in Walju, Aurangabad, India, by Investigator Alicia Mozzachio, Microbiologist Raymond Oji and Chemist Felix Maldonado, during the period of November 8-11, 2005.  The inspection revealed significant deviations from U.S. Current Good Manufacturing Practices (CGMP) in the manufacture of drug products and active pharmaceutical ingredients (API's).  The deviations were listed on an Inspectional Observations (FDA-483) form, issued to you at the close of the inspection.  These CGMP deviations cause your drug products and API's to be adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act.

Our review also included your December 7, 2005 response to the FDA-483 observations.  We believe the following deficiencies need more comprehensive corrections.

1)  Written production and process control procedures were not always followed and documented at the time of performance.   21CFR 211.100 (b)

A.  The process Validation protocol of [redacted] tablets was not followed. (Observation #5 on the FDA-483)  The protocol states [redacted] which results in a sample range of [redacted] to [redacted] mg.  The samples that were taken were documented as 115g, 3.5g and 115g, which are all outside the range allowed in the protocol.  Your response to this deficiency is not adequate in that it states that the 3.5g sample was erroneously documented, and was actually a 35g sample.  This does not address the taking of excess amounts of material for testing.  The investigators also noted that it was unclear in the [redacted] individual samples were maintained separately or combined.  Please demonstrate to us that this protocol is accurate or that a new protocol was carried out correctly.  Also, please provide corrective action for not following approved protocols.

B.  The locations of [redacted] used for environmental monitoring during the execution of Protocol [redacted] were not documented until eight months after the execution of the record.  (Observation #3 on the FDA-483)

Your response states that a drawing of the locations of the [redacted] during the [redacted] effectiveness study was prepared for the investigator; however, this drawing was prepared from memory.  The observation is citing failure to define or document the location of the [redacted] prior to or during the study.  Your response also did not address the issue of preparing and approving validation protocols which lacked this important information.  Relying on the recollection of an employee eight months after the protocol was executed is not good practice.  Further, no preventative actions were submitted for future protocols and studies.

2)  Control records do not include complete and accurate information relating to the production and control of each batch.    21 CFR 211.188

A.  The [redacted] preparation record did not include documentation to confirm the addition of  [redacted] to the [redacted] used for environmental monitoring. (Observation #4 on the FDA-483)

Your response states that the SOP for "Storage, preparation and sterilization of the [redacted] has been revised.  Although the revision of the SOP addresses this problem going forward, your response does not explain how your firm knows whether [redacted] was added to the prior to the revision.  The lack of documentation supporting the addition of [redacted] the environmental monitoring calls into question whether or not this addition did indeed occur, especially since other additions to the [redacted] were documented.  Documentation reviewed during this inspection as well as the last inspection showed extremely low counts on your environmental monitoring.  Without the [redacted] addition to the [redacted] the [redacted] nature of the drug many not have been inhibited.  Please demonstrate that the environmental monitoring of your [redacted] products is representative and accurate, and includes accurate documentation for these products prior to shipment.

B.  The [redacted] logbook did not contain complete and/or accurate documentation.  (Observation #1 on the FDA-483)

Your response indicated that the SOP cited was updated to include the signature of the person performing the operation.  We expect that all entries in logbooks, batch records, laboratory documentation and all other documentation be signed by the person who performed the operation.  Having a supervisor sign does not give the same level of accountability.  Your response did not contain a global evaluation of other logbooks where entries may be performed similarly.

Complete, true and accurate records are the foundation for good GMPs.  Reliable documentation is a control which raises assurance of the quality of the product manufactured.  Violations concerning inadequate documentation are serious and should be handled as such.

We are also concerned that the two previous inspections also noted failure to maintain complete and accurate records, and that your firm may not have taken this type of discrepancy seriously and thus has not corrected the documentation practices of your employees.  In addition, during a regulatory meeting with your firm on May 7, 2004, management indicated to us that inappropriate documentation practices have occurred at your facility.  Practices such as back dating and signing for actions not performed are serious violations.

Failure to correct these deficiencies may result in FDA denying entry of articles manufactured by your firm into the United States.  The articles could be subject to refusal of admission pursuant to Section 801(a)(3) of the Act in that the methods and controls used in their manufacture do not appear to conform to Current Good Manufacturing Practices within the meaning of Section 501(a)(2)(b) of the Act.

Please respond to this letter within 30 days of receipt.  Your response should include data collected in your correction to the deficiencies cited as well as copies of procedures not already included.  Please identify your response with FEI 3004540156. Until FDA can confirm compliance with CGMP's and correction to the most recent inspection deficiencies, this office will recommend disapproval of any new applications listing your firm as the manufacturer of Active Pharmaceutical Ingredients and finished pharmaceutical drug products.  Please contact Carole Jones, Compliance Officer, at the address and telephone numbers shown below, if you have any questions, written response or concerns regarding these decisions.

U.S. Food & Drug Administration
CDER HFD-325
11919 Rockville, Pike
Rockville, MD 20852
Tel: (301) 827-9054; FAX (301) 827-8909

To schedule a re-inspection of your facility, after corrections have been completed and your firm is in compliance with CGMP requirements, send your request to: Director, Division of Field Investigations HFC-130, 5600 Fisher's Lane, Rockville, MD, 20857. You can also contact that office by telephone at (301) 827-5655 or by fax at (301) 443-6919.

Sincerely

 

Nicholas Buhay
Acting Director
Division of Manufacturing and Product Quality
Center for Drug Evaluation and Research