| Dec 21, 2022 | Drugs · Drug Quality Assurance | 6 cited references- 21 CFR 211.192. Investigations of discrepancies, failures There is a failure to thoroughly review any unexplained discrepancy and the failure of a batch or any of its components to meet any of its specifications whether or not the batch has been already distributed.
- 21 CFR 211.188(b). Batch production and Batch Control Record Requirements The batch production and control records are deficient in that they do not include documentation of the accomplishment of each significant step in manufacturing and processing.
- 21 CFR 211.100(b). SOPs not followed / documented Written production and process control procedures are not followed in the execution of production and process control functions.
- 21 CFR 211.84(b). Representative Samples Representative samples are not taken of each shipment of each lot of components for testing or examination.
- 21 CFR 211.56(a). Sanitation--buildings not clean, free of infestation Buildings used in the manufacture, processing, packing or holding of drug products are not maintained in a clean and sanitary condition.
- 21 CFR 211.67(a). Cleaning / Sanitizing / Maintenance Equipment and utensils are not maintained at appropriate intervals to prevent malfunctions that would alter the safety, identity, strength, quality or purity of the drug product.
| Voluntary Action Indicated (VAI) |
| Feb 13, 2019 | Drugs · Drug Quality Assurance | 4 cited references- 21 CFR 211.84(d)(3). Testing Containers & Closures Conformity with Specs Containers and closures are not tested for conformance with all appropriate written procedures.
- 21 CFR 211.166(a). Written program not followed The written stability testing program is not followed.
- 21 CFR 211.42(c)(10)(vi). Equipment to control conditions Aseptic processing areas are deficient regarding systems for maintaining any equipment used to control the aseptic conditions.
- 21 CFR 211.67(c). Cleaning/maintenance records not kept Records are not kept for the maintenance, cleaning, sanitizing and inspection of equipment.
| Voluntary Action Indicated (VAI) |
| May 5, 2017 | Drugs · Drug Quality Assurance | 6 cited references- 21 CFR 211.42(c)(2). Rejected Material Area Separate or defined areas to prevent contamination or mix-ups are deficient regarding operations related to the holding of rejected components, drug product containers, closures and labeling before disposition.
- 21 CFR 211.113(b). Procedures for sterile drug products Procedures designed to prevent microbiological contamination of drug products purporting to be sterile are not established and followed.
- 21 CFR 211.84(d)(3). Establish reliability of supplier's C of A Establishment of the reliability of the container and closure supplier's report of analyses is deficient in that the test results are not appropriately validated at appropriate intervals.
- 21 CFR 211.94(a). Reactive/Additive/Absorptive Containers/Closures Drug product containers or closures are reactive and absorptive so as to alter the safety, identity, strength, quality, and purity of the drug beyond the official or established requirements.
- 21 CFR 314.81(b)(1)(ii). Failure to meet specifications An NDA-Field Alert Report was not submitted within three working days of receipt of information concerning a failure of one or more distributed batches of a drug to meet the specifications established for it in the application.
- 21 CFR 211.42(c)(10)(iv). Environmental Monitoring System Aseptic processing areas are deficient regarding the system for monitoring environmental conditions.
| Voluntary Action Indicated (VAI) |
| Jul 15, 2016 | Drugs · Drug Quality Assurance | 1 cited reference- 21 CFR 211.111. Establishment of time limitations Time limits are not established when appropriate for the completion of each production phase to assure the quality of the drug product.
| Voluntary Action Indicated (VAI) |
| Jul 20, 2015 | Drugs · Drug Quality Assurance | 3 cited references- 21 CFR 211.165(f). Failing drug products not rejected Drug products failing to meet established standards, specifications, and quality control criteria are not rejected.
- 21 CFR 211.160(b). Scientifically sound laboratory controls Laboratory controls do not include the establishment of scientifically sound and appropriate specifications and test procedures designed to assure that components, in-process materials, and drug products conform to appropriate standards of identity, strength, quality and purity.
- 21 CFR 211.110(a). Control procedures to monitor and validate performance Control procedures are not established which validate the performance of those manufacturing processes that may be responsible for causing variability in the characteristics of in-process material and the drug product.
| Voluntary Action Indicated (VAI) |
| Oct 30, 2013 | Drugs · Drug Quality AssuranceDrugs · Bioresearch Monitoring | None posted | Voluntary Action Indicated (VAI) |
| Oct 30, 2013 | Drugs · Drug Quality AssuranceDrugs · Bioresearch Monitoring | 1 cited reference- 21 CFR 211.160(b)(3). Drug products-sampling procedures/specifications Laboratory controls do not include a determination of conformance to appropriate specifications for drug products.
| Voluntary Action Indicated (VAI) |
| Dec 13, 2012 | Drugs · Bioresearch MonitoringDrugs · Drug Quality Assurance; Drugs · Unapproved and Misbranded Drugs | 14 cited references- 21 CFR 211.103. Actual vs. theoretical yields not determined Actual yield and percentages of theoretical yield are not determined at the conclusion of each appropriate phase of processing of the drug product.
- 21 CFR 314.80(c)(2). Late submission of annual safety reports Not all annual periodic adverse drug experience reports have been submitted within 60 days of the anniversary date of the approval of the application.
- 21 CFR 314.80(c)(1)(iv). Failure to identify report content Each post marketing 15-day Alert report submitted to FDA did not have its contents prominently identified, i.e. post marketing 15-day report.
- 21 CFR 314.80(b). Failure to review ADE information Adverse drug experience information obtained or otherwise received from any source was not promptly reviewed, including information from commercial marketing experience.
- 21 CFR 314.80(c). Failure by applicant to report ADE Adverse drug experience information has not been reported to FDA.
- 21 CFR 314.80(j). Failure to maintain records Records relating to all adverse drug experiences known to you, including raw data and any correspondence, have not been maintained for the required ten year period.
- 21 CFR 314.80(b). Failure to develop written procedures Written procedures have not been developed for the surveillance, receipt, evaluation, and reporting to FDA of post marketing adverse drug experiences.
- 21 CFR 211.25(a). GMP Training Frequency GMP training is not conducted on a continuing basis to assure that employees remain familiar with CGMP requirements applicable to them.
- 21 CFR 211.198(a). Complaint Handling Procedure Procedures describing the handling of written and oral complaints related to drug products are deficiently written or followed.
- 21 CFR 314.80(c)(1)(ii). Submission of report follow-up Follow-up reports were not submitted concerning post marketing 15-day reports.
- 21 CFR 211.192. Investigations of discrepancies, failures There is a failure to thoroughly review any unexplained discrepancy and the failure of a batch or any of its components to meet any of its specifications whether or not the batch has been already distributed.
- 21 CFR 314.81(b)(2). Timely submission An annual report was not submitted within 60 days of the anniversary date of U.S. approval of the application to the FDA division responsible for reviewing the application.
- 21 CFR 314.80(c)(2). Late submission of quarterly safety reports Not all quarterly periodic adverse drug experience reports have been submitted within 30 days of the close of the quarter.
- 21 CFR 211.180(e). Records reviewed annually Records are not maintained so that data therein can be reviewed at least annually to evaluate the quality standards of each drug product to determine the need for changes in specifications or manufacturing or control procedures.
| Voluntary Action Indicated (VAI) |
| Oct 19, 2011 | Drugs · Unapproved and Misbranded DrugsDrugs · Drug Quality Assurance | 7 cited references- 21 CFR 211.110(a). Control procedures to monitor and validate performance Control procedures are not established which validate the performance of those manufacturing processes that may be responsible for causing variability in the characteristics of in-process material and the drug product.
- 21 CFR 211.198(a). Complaint Handling Procedure Procedures describing the handling of written and oral complaints related to drug products are deficiently written or followed.
- 21 CFR 211.166(a). Written program not followed The written stability testing program is not followed.
- 21 CFR 211.22(d). Procedures not in writing, fully followed The responsibilities and procedures applicable to the quality control unit are not fully followed.
- 21 CFR 211.63. Equipment Design, Size and Location Equipment used in the manufacture, processing, packing or holding of drug products is not of appropriate design to facilitate operations for its intended use.
- 21 CFR 211.142. Written warehousing procedures established/followed Procedures describing the warehousing of drug products are not established and followed.
- 21 CFR 211.204. Returned drug procedures in writing and followed Procedures describing the of returned drug products are not followed.
| Voluntary Action Indicated (VAI) |
| Nov 12, 2010 | Drugs · Drug Quality Assurance | 9 cited references- 21 CFR 211.160(b)(4). Calibration - at intervals, written program, remedial action The calibration of instruments is not done at suitable intervals in accordance with an established written program and with provisions for remedial action in the event accuracy and/or precision limits are not met.
- 21 CFR 211.194(a)(1). Sample identification and other information Laboratory records do not include the date the sample was received for testing.
- 21 CFR 211.160(b). Scientifically sound laboratory controls Laboratory controls do not include the establishment of scientifically sound and appropriate test procedures designed to assure that drug products conform to appropriate standards of identity, strength, quality and purity.
- 21 CFR 211.22(d). Procedures not in writing, fully followed The responsibilities and procedures applicable to the quality control unit are not fully followed.
- 21 CFR 211.67(b). Written procedures not established/followed Written procedures are not established and followed for the cleaning and maintenance of equipment, including utensils, used in the manufacture, processing, packing or holding of a drug product.
- 21 CFR 211.28(a). Protective Apparel Not Worn Protective apparel is not worn as necessary to protect drug products from contamination.
- 21 CFR 211.113(a). Procedures for non-sterile drug products Procedures designed to prevent objectionable microorganisms in drug products not required to be sterile are not established, written, and followed.
- 21 CFR 211.113(b). Procedures for sterile drug products Procedures designed to prevent microbiological contamination of drug products purporting to be sterile are not established, written, and followed.
- 21 CFR 211.198(b)(2). Complaint Investigation/Follow-Up Findings Complaint records are deficient in that they do not include the findings of the investigation and follow-up.
| Voluntary Action Indicated (VAI) |
| Dec 3, 2009 | Drugs · Drug Quality AssuranceDrugs · Unapproved and Misbranded Drugs | 9 cited references- 21 CFR 211.165(e). Test methods The accuracy, sensitivity, specificity, and reproducibility of test methods have not been established.
- 21 CFR 211.160(b). Scientifically sound laboratory controls Laboratory controls do not include the establishment of scientifically sound and appropriate standards designed to assure that drug products conform to appropriate standards of identity, strength, quality and purity.
- 21 CFR 211.84(d)(2). Reports of Analysis (Components) Reports of analysis from component suppliers are accepted in lieu of testing each component for conformity with all appropriate written specifications, without establishing the reliability of the supplier's analyses through appropriate validation of the supplier's test results at appropriate intervals.
- 21 CFR 211.67(a). Cleaning / Sanitizing / Maintenance Equipment and utensils are not cleaned at appropriate intervals to prevent contamination that would alter the safety, identity, strength, quality or purity of the drug product.
- 21 CFR 211.188. Prepared for each batch, include complete information Batch production and control records do not include complete information relating to the production and control of each batch.
- 21 CFR 211.160(b)(3). Drug products-sampling procedures/specifications Laboratory controls do not include a determination of conformance to appropriate specifications for drug products.
- 21 CFR 211.160(b)(1). Incoming lots - conformance to written specs- Laboratory controls do not include determination of conformance to appropriate written specifications for the acceptance of each lot within each shipment of components used in the manufacture, processing, packing, or holding of drug products.
- 21 CFR 211.110(a). Control procedures to monitor and validate performance Control procedures are not established which validate the performance of those manufacturing processes that may be responsible for causing variability in the characteristics of in-process material and the drug product.
- 21 CFR 211.165(a). Testing and release for distribution Testing and release of drug product for distribution do not include appropriate laboratory determination of satisfactory conformance to the final specifications prior to release.
| Official Action Indicated (OAI) |
| Mar 16, 2009 | Drugs · Bioresearch Monitoring | None posted | No Action Indicated (NAI) |
| Nov 4, 2008 | Drugs · Drug Quality Assurance | None posted | Voluntary Action Indicated (VAI) |
