- California Pharmacy & Compounding Center - Company
July 16, 2015
TO: US FDA Los Angeles District Office (LOS-DO)
ATTENTION: Mr. William Vitale, Compliance Officer
19701 Fairchild, Irvine, CA 92612-2506
Fax: (949) 608-2919
SUBJECT: Response to FDA Warning Letter WL# 23-15, Issued 06/17/15
Request to post FDA Warning Letter WL# 23-15 Response
FEI Number: 3004600090, California Pharmacy & Compounding Center
FDA Inspection Dates: 08/18/2014 - 08/25/2014
Dear Officer Vitale,
California Pharmacy & Compounding Center takes the FDA Warning Letter (WL# 23-15 dated June 17, 2015) very seriously and commits ourselves to address your concerns adequately and expeditiously. We write today to assure the FDA that we understand the critical nature of the deficiencies observed at California Pharmacy & Compounding Center and we are correcting all of them, with particular emphasis on aseptic processing (sterile compounding) to ensure a high level of sterility assurance and contamination control. In addition, we assessed and took immediate actions to correct all labeling concerns and improve the overall labeling process and label control.
We have undertaken a comprehensive assessment of our operations, including facility design, procedures, personnel, processes, materials, and systems. To this end, as per your recommendations, we have retained independent consultants to assess our quality system in great detail and help establish and maintain a comprehensive quality improvement plan that addresses all systemic, technical, and compliance issues. The consultants' expertise encompasses aseptic processing, pharmaceutical quality systems, regulatory compliance, and microbiology. We have attached their CVs for your review. (Appendix A- Consultant CVs)
We are taking corrective actions to remediate critical concerns and have attached a quality improvement plan that summarizes the steps being taken to complete all corrective and preventive actions, thereby fully optimizing our quality and sterile operations over the next six months, and creating a customer focused continuous improvement culture at California Pharmacy & Compounding Center.
California Pharmacy & Compounding Center's drug product labels now include:
1. Some of your facility's drug product labels do not include the name, address, and phone number of your facility; dosage form and strength; a statement of quantity or volume, as appropriate; the date the drug was compounded; expiration date; and storage and handling instructions.
2. Some of your drug product labels do not include the statements, "This is a compounded drug" and "Not for Resale," and the labels of the drugs that you dispense or distribute other than pursuant to a prescription for an individual identified patient do not include the statement "Office Use Only."
3. Some of the container labels of your drug products do not include the following information to facilitate adverse event reporting: www.fda.gov/medwatch and 1-800-FDA-1088."
• Furthermore, in our enhanced policies and procedures, we have developed a process to continue thoroughly monitoring future drug products for all FDA required labels. Please see Packaging and Labeling section in the attached Quality Improvement Plan Summary for more details. (Labeling procedure complete; see attached Appendix B - SOP 8.10 Sterile Preparation Labeling. Monitoring Procedure is ongoing.)
• Magnahelic gauges measuring pressure differentials are labeled, calibrated, and have been repositioned in a highly visible area next to the entrance to the class ified area. Pressure differential measurements are monitored and recorded during daily production periods. Please see attached pictures. (See Appendix C- Magnahelic Gauges Pictures)
Independent consultants and the Management of California Pharmacy & Compounding Center completed a comprehensive review of the aseptic processing operations, environmental controls, and monitoring programs. The following are responses to the observations of Warning Letter WL# 23-15:
1. Your firm failed to establish and follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile, and that include validation of all aseptic and sterilization processes [21 CFR 211.113(b)].
• In an ongoing effort to enhance our written procedures designed to prevent microbiological contamination of sterile drug products, a step-by-step review and risk assessment of each unique aseptic process will be conducted. The results of those reviews will be integrated into log formula worksheets (batch records) and associated policy and procedure documents for sterility assurance and resulting training and qualification programs.
2. Your firm failed to ensure that manufacturing personnel wear clothing appropriate to protect drug product from contamination [21 CFR 211.28(a)].
• California Pharmacy & Compounding Center has implemented appropriate sterile gowning procedures including the use of sterile goggles to prevent drug product from contamination. All employees have been trained on revised gowning procedures. Gowning re-training completed.
3. Your firm failed to establish an adequate system for monitoring environmental conditions in aseptic processing areas [21 CFR 211.42(c)(10)(iv)].
• A formal risk assessment was performed to select optimal sampling locations, maximizing the efficacy of our Environmental Monitoring program. Per this review, we have substantially increased monitoring of the classified areas and personnel since 10/17/14 inspection, and will continue to increase environmental sampling so that samples are collected on a per-batch basis. All tests, including smoke studies, are performed under dynamic conditions. (See Appendix D-Quality Improvement Plan Summary. Implementation of increased Environmental Monitoring program is 2 weeks after receipt of additional testing equipment)
4. Your firm failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed [21 CFR 211.192].
• We are upgrading our deviation process such that it is comprehensive and includes all internal deviations to, processes, procedures, and tests. Customer communication such as complaints and potential Adverse Events will be investigated through a separate process and set of procedures. (Implementation upon completion of procedures in November 2015)
5. Your firm failed to establish an adequate system for maintaining equipment used to control the aseptic conditions [21 CFR 211.42(c)(10)(vi)].
• The management of California Pharmacy & Compounding Center is requesting quotes for single use sterile depyrogenated equipment and utensils. Internal sterilization and depyrogenation cycles will no longer be performed on equipment and utensils. (Implementation is 1 month after receipt of disposable equipment and utensils)
The management of California Pharmacy & Compounding Center understands that corrective actions need to be comprehensive both from a technical standpoint as well as the supporting quality systems. A broad comprehensive review of our entire sterile operations was undertaken and we believe the actions outlined in the attached quality improvement plan demonstrate systemic corrective and preventive changes.
For example, on the subject of media fill design and execution, with the assistance of an aseptic processing SME, we inventoried all sterile compounds and aseptic processes. We grouped items by multiple factors including, but not limited to, process, container, contamination risk, complexity, units filled, processing time, et c. From this matrix, we developed a comprehensive plan that now includes 11 different media fill protocols to demonstrate validation of all of our aseptic processes. (See Appendix E-Media Fill Program Matrix)
In conclusion, the management of California Pharmacy & Compounding Center believe that the immediate actions we have taken, as well as the ongoing quality improvements we are undertaking, will demonstrate compliance with FDA current Good Manufacturing Practice: Interim Guidance for Human Drug Compounding Facilities Under Section 503B of the FD&C Act (July 2014); FDA Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing Current Good Manufacturing Practices (September 2004); and all other applicable industry standards. Patient safety is our highest priority and we will demonstrate to the FDA that we are working diligently to establish a robust quality assurance plan and continuous quality improvement program.
Thank you, Officer Vitale, for reviewing our response to Warning Letter WL# 23-15. We invite your feedback, and welcome the opportunity to speak with you by phone or meet with you in person or at your offices should that be necessary. We request that our response be posted on the FDA Internet website. We greatly appreciate your time on this matter.
Glen A. Olsheim, Chief Financial Officer
California Pharmacy and Compounding Center
4000 Birch Street, Suite 120
Newport Beach, CA 92660-2258
Alonza E. Cruse, Director
Los Angeles District
Virginia Herold, Executive Officer
California State Board of Pharmacy
1625 N. Market Boulevard, Suite N-219
Sacramento, CA 95834
David M. Mazzera, Ph.D.
Chief, Food and Drug Branch
California Department of Public Health
1500 Capital Avenue, MS-7602
Sacramento, California 95899-7413