Inspections, Compliance, Enforcement, and Criminal Investigations
Carlsbad Technology, Inc 04-Oct-01
DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
Food and Drug Administration
19900 MacArthur Blvd., Ste 300
Irvine, California 92612-2445
Telephone (714) 798-7600
RETURN RECEIPT REQUESTED
October 4, 2001
Kuo-Liang (Kevin) Ho
Carlsbad Technology, Inc
5923 13alfour Court
Carlsbad, CA 92008
Dear Mr. Ho:
During an inspection of your pharmaceutical manufacturing facility conducted from August 6 to 17, 2001, our investigators found significant deviations horn the current Good Manufacturing Practice (cGMP) for Finished Pharmaceuticals Regulations (Title 21, Code of Federal Regulations (CFR), Ruts 210 and 211). These deviations 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) as follows:
1. Failure to ensure that any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications shall be thoroughly investigated (21 CFR 211.192). Specifically, our investigation disclosed several instances of temperature and relative humidity excursions of drug products designated for stability testing and stored under controlled conditions were not thoroughly investigated to determine if the excursions had compromised those affected drug products.
2. Failure to ensure that laboratory records include complete data derived from all tests necessary to assure compliance with established specifications and any testing and standardization of laboratory reference standards, reagents and standard solutions (21 CFR 211.194). Specifically, our investigation disclosed several instances where there is no description of samples or standards preparation, the lot number of standards used, or description of buffers used to calibrate laboratory equipment. Additionally, our investigation disclosed several instances where suitability of all testing methods and qualification of laboratory testing equipment could not be verified under actual use conditions or no documentation could be provided to support the usage and maintenance of several pieces of laboratory equipment.
3. Failure to assure batch uniformity and product integrity by establishing and following written procedures that describe the in-process controls, tests, or examinations to be conducted on appropriate samples of in-process materials of each batch. Such ?control procedures shall be established to monitor the output and to validate the performance of these manufacturing processes that may be responsible for causing variability in the characteristics of in-process material and the product [21 CFR 211.110]. Specifically, there are no specified holding times for final blends prior to tableting or encapsulation or holding times for in-process tablets or capsules prior to coating or packaging. Additionally, specified tablet press speeds were changed during the production of three lots of drug products without any written justification for the changes.
4. Failure to ensure that cleaning methods used in cleaning production equipment will sufficiently prevent contamination that would alter the safety, identity, strength, quality, or purity of drug products [21 CFR 211.67]. Specifically, no documented evidence exists to demonstrate the effectiveness of cleaning methods and agents used in cleaning production equipment to ensure that residues have been reduced to acceptable levels.
We acknowledge that you have submitted to this office written responses to the form FDA-483. We have reviewed your responses and while these responses address several of our concerns, there still remain several issues that could not be completely evaluated because the supporting documentation was not submitted with your responses or the responses were inadequate. Detail comments are listed on Attachment A to this letter.
We also acknowledge your request for a face-to-face meeting with the District to discuss the results of our investigation and your proposed connective and preventive actions. We are prepared to discuss these issues with your firm. Please contact Senior Compliance Officer, Dannie E. Rowland at (949) 798-7649 to make the necessary arrangements.
The above identification of violations is not intended to be an all-inclusive list of deficiencies at your facility. A list of observations (FDA 483) was issued and discussed with you at the conclusion of the inspection. It is your responsibility to assure adherence with each requirement of the Good Manufacturing Practice regulation and other applicable regulations. Federal agencies are advised of the issuance of all warning letters about drugs and devices so that they may take this information into account when considering the award of contracts.
You should take prompt action to correct these deviations. Failure to do so may result in regulatory action without further notice, including seizure and/or injection. You should notify this office in writing, within fifteen (15) working days of receipt of this letter, of the specific steps you have taken to correct the noted violation, including an explanation of each step taken to prevent the recurrence of similar violations. If corrective action cannot be completed within (15) working days, state the reason for the delay and time within which the corrections will be completed.
Your reply should be addressed to:
Thomas Sawyer, Director of Compliance
U.S. Food and Drug Administration
19900 MacArthur Blvd., Suite. 300
Irvine, CA 92612
Alonza E. Cruse