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Inspectional Findings/Warning Letters . Vickie Anderson Supervisory Investigator Los Angeles District USP WCDG & AOAC-SCS Joint Two-Day 5/8-9/14 Regulatory & Compliance Conference, US FDA/Irvine CA. Today’s Objectives. Inspectional trends Warning Letters trends. Cited Areas.
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Inspectional Findings/Warning Letters Vickie Anderson Supervisory Investigator Los Angeles District USP WCDG & AOAC-SCS Joint Two-Day 5/8-9/14 Regulatory & Compliance Conference, US FDA/Irvine CA
Today’s Objectives • Inspectional trends • Warning Letters trends
3-year Top Ten Drug Observations 10/01/2011 And 09/30/2012 10/01/2012 And 09/30/2013) 211.22(d) 211.22(d) 211.192 211.100(a) 211.100(a) 211.192 211.22(d) 211.100(b) 211.160(b) As of 04/17/2014
Records and Reports Failure to thoroughly review any unexplained discrepancy Failure to thoroughly review failure of a batch or component to meet specification
Records and Reports, Specifically , batch of Oral Solution (lot #) was released without an adequate investigation (i.e., considering the possible effect of contamination) when a cloth-like towel was found to have been in the mixing tank during batch processing.
Organization and Responsibilities Quality Control Unit responsibilities and procedures are Not written Not fully followed
Organization and Responsibilities, Specifically , the quality control unit allowed the release of five lots of drug products for distribution even though the Material on Hold forms had not been reviewed/approved by the Release Coordinator as required by Standard Operating Procedure (Material On Hold Procedure). In addition, there were multiple instances where your quality control unit released batches prior to the closure of investigations of non-conforming product and OOS results.
Laboratory Controls No establishment of scientifically sound and appropriate Specifications Sampling plans Test procedures
Laboratory Controls, Specifically ,there was no scientific justification for sampling plans for environmental monitoring in areas where terminally sterilized injectable are manufactured. This includes the frequency and locations of viable airborne particulate sampling activities, the locations of non-viable airborne particulate sampling activities, the frequency and locations of non-product contact surface monitoring, and the evaluation of microorganisms found through environmental monitoring activities. In addition, the environmental monitoring records do not identify the locations from which environmental monitoring samples were taken.
Production and Processes, Written production and process control procedures are not followed in the execution of process control functions, documented at the time of performance.
Production and Processes, Specifically , glass fragments were present during the manufacturing of Batch #. Glass fragments were observed in the Assembly area where open glass vials are inserted into the outer plastic sheaths and move uncovered on the conveyance mechanism.
Equipment No written procedures Not following written procedures
Equipment, Specifically , failure to evaluate the effectiveness of your cleaning procedures. You do not have data to show that your equipment cleaning procedure is adequate to prevent cross-contamination. You have not conducted cleaning validation, cleaning verification, or swab recovery studies for multi-use equipment used in the production of OTC drug products.
Example: What’s showing up in Warning Letters? GMP Your firm failed to exercise appropriate controls over computer or related systems to assure that only authorized personnel institute changes in master production and control records, or other records (21 CFR 211.68 (b))
Example: What’s showing up in Warning Letters? GMP QC laboratory computerized instruments were found to be stand-alone, and laboratory personnel demonstrated that they can delete electronic raw data files from the local hard drive. Multiple HPLC data files in 2013 - deleted No unique user names and passwords
Example: What’s showing up in Warning Letters? GMP Failure to establish and follow appropriate written procedure designed to prevent microbiological contamination of drug product purporting to be sterile and that include validation of all aseptic and sterilization processes (21 CFR 211.113(b)) Non-integral and non-sterile gloves are used for aseptic processing Visible holes and flaking gloves
Example: What’s showing up in Warning Letters? CYBER Promotion FDA’s review of your website has determined…. Generic-----is a proprietary name of an FDA-approved drug known to treat disease (influenza). Your product (oseltamivir phosphate) is a drug. No approved application R/X offered for sale on website
Example: What’s showing up in Warning Letters? CYBER Promotion The United States Food and Drug Administration (FDA) recently reviewed your websites (listed in the table at the bottom of this letter) and has determined that your websites offer products for sale in violation of the Federal Food, Drug, and Cosmetic Act (FD&C ACT)…. offer unapproved and misbranded new drugs for sale in violation of sections…. We request that you immediately cease marketing violative drug products to United States consumers.
A Reason For Cyber Warning Letters…. Inherent risk in buying unapproved and misbranded new drugs. Unapproved new drugs from unregulated sources do not have the same assurance of safety and effectiveness as those drugs subject to FDA oversight, and such drugs have been found to be contaminated, counterfeit, contain varying amounts of active ingredients, or contain different ingredients altogether.
Conclusion Consider this information to improve operations.
