| Public Health Service Food and Drug Administration |
| Silver Spring MD 20993 |
Department of Health and Human ServicesWarning Letter
VIA UPS MAIL
WL: 320-10-008
August 23, 2010
Mr. Gurdeep Singh, Joint Managing Director
Stericon Pharma Pvt. Ltd.
#9R, Sub Layout of Plot No.9, 1st Phase, Bommasandra Indl. Area
Bangalore, Karnataka 560 099
India
Dear Mr. Singh:
As a result of our March 12, 15 - 17, 2010 inspection of your drug manufacturing facility, Stericon Pharma Pvt. Ltd., #9R, Sub Layout of Plot No.9, 1st Phase, Bommasandra Indl.. Area, Bangalore, Karnataka 560 099 India, we have identified significant violations of Current Good Manufacturing Practice (CGMP) regulations for Finished Pharmaceuticals, Title 21, Code of Federal Regulations, Parts 210 and 211. These violations cause your drug products 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.
Specific violations include, but are not limited, to the following:
1. Your firm has not established separate or defined areas or such other control systems to prevent contamination during aseptic processing (21 C.F.R. § 211.42(c)]. For example,
a. Your environmental monitoring program does not provide assurance that environmental contaminants are reliably detected. Examples of deficient procedures and practices include: failure to conduct active (viable) air sampling during filling operations, failure to conduct non-viable particulate sampling during filling operations, and failure to have a suitable method for identification of environmental isolates.
Your firm needs to establish an adequate environmental monitoring program. It should capture meaningful data, and act as an early warning system to detect possible environmental contaminants that may impact the sterility of the ophthalmic drug products manufactured at your facility that purport to be sterile.
b. There is no documentary evidence of in-situ air pattern analysis (e.g., smoke studies) conducted at critical areas to demonstrate unidirectional airflow and sweeping action over and away from the product under dynamic conditions. Please note that proper design and control prevents turbulence and stagnant air in the critical area. It is crucial that you evaluate airflow patterns for turbulence that can act as a channel for air contamination. The studies should be well documented with written conclusions, and evaluate impact of aseptic manipulations (e.g., interventions) and equipment design.
c. Your procedure for monitoring differential pressures within the aseptic processing areas is not sufficient. It is vital for rooms of higher air cleanliness to have an appropriate and substantial pressure differential relative to adjacent rooms of lower air cleanliness. Pressure differentials between cleanrooms should be monitored continuously throughout each shift and frequently recorded. All alarms should be documented, and deviations from established limits should be investigated.
2. Your firm failed to ensure that each person engaged in the manufacture, processing, packing, or holding of a drug product has the education, training, and experience, or any combination thereof, to enable that person to perform the assigned functions.
(21 C.F.R. § 211.25(a)]. For example,
There are no procedures for the qualification of operators who conduct operations within the aseptic processing areas. This includes deficiencies related to an ongoing evaluation for conformance to written procedures for aseptic techniques, and an aseptic gowning qualification program. Your firm should establish a training program that includes an initial assessment, routine evaluation, timeframes for re-qualification, and more frequent qualification activities, when warranted.
In addition to the items listed above, the inspection uncovered additional deficiencies that increase our concerns regarding the quality of the sterile ophthalmic drug products manufactured at your facility. These issues include, but are not limited, to:
• failure to provide complete documentation for validation of autoclave cycles intended to sterilize equipment and utensils used in aseptic processing operations
• discrepancies between the equipment qualification documentation and the batch record regarding critical process parameters (i.e., mixing speeds)
• failure to monitor storage conditions for raw materials, components, and finished drug product.
It is important that you take appropriate actions to address these deficiencies and notify us of what actions you will take against all lots of sterile ophthalmic drug products that were manufactured at your Bangalore facility, which may still be available for use in the United States.
The violations cited in this letter are not intended to be an all-inclusive statement of violations that exist at your facility. You are responsible for investigating and determining the causes of the violations identified above and for preventing their recurrence and the occurrence of other violations. If you wish to ship your products 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 violations and your firm's compliance with CGMP, FDA may withhold approval of any new applications or supplements listing your firm as a drug product manufacturer. In addition, FDA will be refusing admission of articles manufactured at Stericon Pharma Pvt. Ltd., #9R, Sub Layout of Plot No.9, 1st Phase, Bommasandra Indl. Area, Bangalore, Karnataka 560 099 India 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 violations. Include an explanation of each step being taken to prevent the recurrence of violations 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 # 3004983128.
If you have questions or concerns regarding this letter, contact Douglas Campbell, Compliance Officer, at the below address and telephone number.
U.S. Food and Drug Administration
Center for Drug Evaluation and Research
Division of Manufacturing and Product Quality
International Compliance Branch
White Oak, Building 51, Room 4224
10903 New Hampshire Ave
Silver Spring, MD 20993
Tel: (301) 796-3201
Fax: (301) 847-8741
Sincerely,
/S/
/Richard L. Friedman/
Richard L. Friedman
Director
Division of Manufacturing and Product Quality
Office of Compliance
Center for Drug Evaluation and Research
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