USFDA WARNING LATTER 2019 – DRUGS
| Reference Number | Short Description | Critical Observation and discripancies |
| 21 CFR 211.22(d) | Procedures not in writing, fully followed | The responsibilities and procedures applicable to the quality control unit are not in writing and fully followed. |
| 21 CFR 211.192 | Investigations of discrepancies, failures | There is a failure to thoroughly review any unexplained discrepancy, 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 211.160(b) | Scientifically sound laboratory controls | Laboratory controls do not include the establishment of scientifically sound and appropriate specifications ,standards, sampling plans, test procedures, designed to assure that components, drug product containers,closures,in-process materials, labelling, drug products conform to appropriate standards of identity, strength, quality and purity. |
| 21 CFR 211.100(a) | Absence of Written Procedures | There are no written procedures for production and process controls designed to assure that the drug products have the identity, strength, quality, and purity they purport or are represented to possess. |
| 21 CFR 211.67(a) | Cleaning / Sanitizing / Maintenance | Equipment and utensils are not cleaned,maintained,sanitized at appropriate intervals to prevent/ malfunctions/contamination that would alter the safety, identity, strength, quality or purity of 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, identity and strength of each active ingredient prior to release. |
| 21 CFR 211.110(a) | Control procedures to monitor and validate performance | Control procedures are not established which monitor the output ,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 211.113(b) | Procedures for sterile drug products | Procedures designed to prevent microbiological contamination of drug products purporting to be sterile are not established /written /followed. |
| 21 CFR 211.68(b) | Computer control of master formula records | Appropriate controls are not exercised over computers or related systems to assure that changes in master production and control records or other records are instituted only by authorized personnel. |
| 21 CFR 211.166(a) | Lack of written stability program | There is no written testing program designed to assess the stability characteristics of drug products. |
| 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 of adequate size, suitably located to facilitate operations for its intended use, cleaning and maintenance. |
| 21 CFR 211.67(b) | Written procedures not established/followed | Written procedures are not established followed for the cleaning and maintenance of equipment, including utensils, used in the manufacture, processing, packing or holding of a drug product. Specifically. |
| 21 CFR 211.68(a) | Calibration/Inspection/Checking not done | Routine calibration,inspection,checking of automatic mechanical electronic equipment is not performed according to a written program designed to assure proper performance. |
| 21 CFR 211.25(a) | Training–operations, GMPs, written procedures | Employees are not given training in the particular operations they perform as part of their function current good manufacturing practices written procedures required by current good manufacturing practice regulations. |
| 21 CFR 211.42(c)(10)(iv) | Environmental Monitoring System | Aseptic processing areas are deficient regarding the system for monitoring environmental conditions. |
| 21 CFR 211.165(e) | Test methods | The accuracy ,sensitivity, specificity, reproducibility of test methods have not been established, documented. |
| 21 CFR 211.188 | Prepared for each batch, include complete information | Batch production and control records are not prepared for each batch of drug product produced, do not include complete information relating to the production and control of each batch. |
| 21 CFR 211.113(b) | Validation lacking for sterile drug products | Procedures designed to prevent microbiological contamination of drug products purporting to be sterile did not include adequate validation of the aseptic, sterilization process. |
| 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, documented at the time of performance. |
| 21 CFR 211.160(a) | Following/documenting laboratory controls | Established specifications, standards, sampling plans, test procedures, laboratory control mechanisms are not followed and documented at the time of performance. |
| 21 CFR 211.25(a) | Training , Education , Experience overall | Employees engaged in the manufacture, processing, packing, holding of a drug product lack the education, training,experience required to perform their assigned functions. |
| 21 CFR 211.194(a) | Complete test data included in records | Laboratory records do not include complete data derived from all tests, examinations and assay necessary to assure compliance with established specifications and standards. |
| 21 CFR 211.42(c)(10)(v) | Cleaning System | Aseptic processing areas are deficient regarding the system for cleaning and disinfecting the room, equipment to produce aseptic conditions. |
| 21 CFR 211.192 | Written record of investigation incomplete | Written records of investigations into unexplained discrepancies, the failure of a batch or any of its components to meet specifications do not always include the conclusions and follow-up. |
| 21 CFR 211.198(a) | Procedures to be written and followed | Procedures describing the handling of all written and oral complaints regarding a drug product are not established,written,followed. |
| 21 CFR 211.67(b) | Written procedures fail to include | Written procedures for cleaning and maintenance fail to include assignment of responsibility, maintenance and cleaning schedules, description in sufficient detail of methods, equipment and materials used description in sufficient detail of the methods of disassembling and reassembling equipment as necessary to assure proper cleaning and maintenance, instructions for removal or obliteration of previous batch identification, instructions for protection of clean equipment from contamination prior to use, parameters relevant to the operation. |
| 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 211.166(a) | Written program not followed | The written stability testing program is not available and followed. |
| 21 CFR 211.180(e)(2) | Items to cover on annual reviews | Written procedures are not established, followed for evaluations done at least annually and including provisions for a review of complaints, recalls, returned or salvaged drug products, investigations conducted for each drug product. |
| 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 performing at least one specific identity test on each component establishing the reliability of the supplier’s analyses through appropriate validation of the supplier’s test results at appropriate intervals. |
| 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, processing, packing, holding. |
| 21 CFR 211.192 | No written record of investigation | Written records are not always made of investigations into unexplained discrepancies the failure of a batch or any of its components to meet specifications. |
| 21 CFR 211.194(a)(4) | Complete Test Data | Laboratory records are deficient in that they do not include a complete record of all data obtained during testing. |
| 21 CFR 211.170(b) | Annual visual exams of drug products | Reserve samples from representative sample lots or batches of drug products selected by acceptable statistical procedures are not examined visually at least once a year for evidence of deterioration. |
| 21 CFR 211.125(a) | Strict control not exercised over labeling issued | Strict control is not exercised over labelling issued for use in drug product labelling operations. |
| 21 CFR 211.137(a) | Expiration date lacking | Drug products do not bear an expiration date determined by appropriate stability data to assure they meet applicable standards of identity, strength, quality and purity at the time of use. |
| 21 CFR 211.166(a)(3) | Valid stability test methods | The written stability program for drug products does not include reliable, meaningful, specific test methods. |
| 21 CFR 211.192 | Extent of discrepancy, failure investigations | Investigations of an unexplained discrepancy, a failure of a batch or any of its components to meet any of its specifications did not extend to [other batches of the same drug product, other drug products that may have been associated with the specific failure or discrepancy. |
| 21 CFR 211.198(a) | Complaint Handling Procedure | Procedures describing the handling of written and oral complaints related to drug products are not written or followed, deficiently written or followed. |
| 21 CFR 211.25(a) | GMP Training Frequency | GMP training is not conducted on a continuing basis with sufficient frequency to assure that employees remain familiar with CGMP requirements applicable to them. |
| 21 CFR 211.165(b) | Microbiological testing | Each batch of drug product required to be free of objectionable microorganisms is not tested through appropriate laboratory testing. |
| 21 CFR 211.142(b) | Storage under appropriate conditions | Drug products are not stored under appropriate conditions of temperature, humidity, light so that their identity, strength, quality, and purity are not affected. |
| 21 CFR 211.160(a) | Deviations from laboratory control requirements | Deviations from written specifications, standards, sampling plans, test procedures, laboratory mechanisms are not recorded, justified. |
| 21 CFR 211.80(a) | Procedures To Be in Writing | Written procedures are lacking which describe in sufficient detail the receipt ,identification,storage,handling,sampling,testing,approval.rejection] of components, drug product containers, closures. |
| 21 CFR 211.160(a) | Lab controls established, including changes | The establishment of specifications, standards, sampling plans, test procedures, laboratory control mechanisms including any changes thereto, are not drafted by the appropriate organizational unit reviewed and approved by the quality control unit. |
| 21 CFR 211.58 | Buildings not maintained in good state of repair | Buildings used in the manufacturing, processing, packing, holding of a drug product are not maintained in a good state of repair. |
| 21 CFR 211.22(a) | Authority lacking to review records, investigate errors | The quality unit lacks authority to review production records to assure that no errors have occurred, fully investigate errors that have occurred. |
| 21 CFR 211.22(c) | Approve or reject procedures or specs | The quality unit lacks responsibility to approve, reject all procedures or specifications impacting on the identity, strength, quality, purity of drug products. |
| 21 CFR 211.67(c) | Cleaning/maintenance records not kept | Records are not kept for the maintenance, cleaning, sanitizing, and inspection of equipment. |
| 21 CFR 211.182 | Written records kept in individual logs | Written records of major equipment cleaning, maintenance, use are not included in individual equipment logs. |
| 21 CFR 211.192 | Quality unit review of records | Drug product production and control records, are not reviewed, approved by the quality unit to determine compliance with all established, approved written procedures before a batch is released or distributed. |
| 21 CFR 211.46(b) | Equipment for Environmental Control | Equipment for adequate control over air pressure, micro-organisms, dust, humidity, temperature is not provided when appropriate for the manufacture, processing, packing or holding of a drug product. |
| 21 CFR 211.160(b)(3) | Acceptance of drug products | Determinations of conformance to appropriate written specifications for acceptance are not made, deficient for drug products. |
| 21 CFR 211.160(b)(4) | Calibration – at intervals, written program, remedial action | The calibration of instruments apparatus gauges recording devices is not done at suitable intervals in accordance with an established written program with provisions for remedial action in the event accuracy and or precision limits are not met. |
| 21 CFR 211.22(a) | Approve or reject components, products | The quality unit lacks the responsibility and authority to approve reject all components, drug product containers, closures, in process materials, packaging material,labelling,drug products. |
| 21 CFR 211.28(a) | Clothing appropriate for duties performed | Clothing of personnel engaged in the manufacturing ,processing,packing,holding of drug products is not appropriate for the duties they perform. |
| 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. |
| 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, free of infestation by rodents, birds insects, and other vermin. |
| 21 CFR 211.100(b) | Procedure Deviations Recorded and Justified | Deviations from written production and process control procedures are not recorded, justified. |
| 21 CFR 211.42(c) | Defined areas of adequate size for operations | The separate or defined areas, control systems necessary to prevent contamination or mix-ups are deficient. |
| 21 CFR 211.80(b) | Handling and Storage to Prevent Contamination | There was a failure to handle and store components, drug product containers, closures at all times in a manner to prevent contamination. |
| 21 CFR 211.100(a) | Changes to Procedures Not Reviewed, Approved | Changes to written procedures are not drafted, reviewed and approved by the appropriate organizational unit reviewed and approved by the quality unit. |
| 21 CFR 211.186(b)(9) | Complete instructions, procedures, specifications et. | Master production and control records lack complete manufacturing and control instructions, sampling and testing procedures, specifications, special notations, precautions to be followed. |
| 21 CFR 211.67(b)(3) | Cleaning SOPs/instructions | Procedures for the cleaning and maintenance of equipment are deficient regarding sufficient detail of the methods, equipment, and materials used in the cleaning and maintenance operation, and the methods of disassembly and reassembling equipment as necessary to assure proper cleaning and maintenance. |
| 21 CFR 211.68(b) | input/output verification | Input to and output from the computer, related systems of formulas, records or data are not checked for accuracy. |
| 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. |
| 21 CFR 211.160(b)(4) | Establishment of calibration procedures | Procedures describing the calibration of instruments, apparatus, gauges and recording devices are not written or followed deficiently written or followed. |
| 21 CFR 211.84(d)(2) | Testing Each Component for Conformity with Specs | Each component is not tested for conformity with all appropriate written specifications for purity, strength, and quality. |
| 21 CFR 211.142 | Written warehousing procedures established/followed | Procedures describing the warehousing of drug products are not established followed. |
| 21 CFR 212.20(e) | Written QA procedures established, followed | You did not establish, follow written quality assurance procedures. |
| FDCA 501(a)(2)(A) | Use of non-pharmaceutical grade components | You used a non-pharmaceutical grade component in the formulation of a drug product. |
| 21 CFR 211.84(d)(1) | Identity Testing of Each Component | The identity of each component of a drug product is not verified by conducting at least one test to verify the identity, using specific identity tests if they exist. |
| 21 CFR 211.180(c) | Records not made readily available to FDA | Records associated with drug product components ,containers ,closures ,labelling,production,control,distribution and within the retention period for such records, were not made readily available for authorized inspection. |
| 21 CFR 211.198(b)(2) | Written record of complaint to include findings, follow-up | Written records of investigation of a drug complaint do not include the findings of the investigation, the follow-up. |
| FDCA 501(a)(2)(A) | Air flow quality, higher classified area | Your facility design allowed the influx of poor quality air into a higher classified area. |
| 21 CFR 212.30(a) | Orderly handling, prevention of mix-ups, prevention of contamination | Your facilities are not adequate to ensure the orderly handling of materials and equipment the prevention of mix-ups,the prevention of contamination of equipment or product by substances, personnel, or environmental conditions that could reasonably be expected to have an adverse effect on product quality. |
| 21 CFR 211.42(c)(10) | Aseptic Processing Area | Separate or defined areas to prevent contamination or mix-ups are deficient regarding operations related to aseptic processing of drug products. |
| 21 CFR 211.165(f) | Failing drug products not rejected | Drug products failing to meet established standards, specifications.quality control criteria are not rejected. |
| 21 CFR 211.110(a) | Written in-process control procedures | Written procedures are not established followed that describe the in-process controls tests, examinations to be conducted on appropriate samples of in-process materials of each batch. |
| 21 CFR 211.80(a) | Written Procedures Not Followed | Written procedures are not followed for the receipt,identification,storage,handling,sampling,testing,approval,rejection of components drug product containers closures. |
| 21 CFR 211.166(a) | Results not used for expiration dates, storage condition. | Results of stability testing are not used in determining appropriate storage conditions ,expiration dates. |
| 21 CFR 211.67(b)(2) | Cleaning SOPs/schedules | Procedures for the cleaning and maintenance of equipment are deficient regarding maintenance and cleaning schedules, including, where appropriate, sanitizing schedules. |
| 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 manufacturing, processing, packaging, holding] of the drug product. |
| 21 CFR 211.42(c)(10)(i) | Floors, walls, ceiling surfaces | Processing areas are deficient in that floors, walls, ceilings are not smooth and/or hard surfaces that are easily cleanable. |
| 21 CFR 211.42(c)(10)(iii) | Air Supply | Processing areas are deficient regarding air supply that is filtered through high-efficiency particulate air filters under positive pressure. |
| 21 CFR 211.180(e)(1) | Review of representative number of batches | Written procedures are not established followed for evaluations conducted at least annually to review records associated with a representative number of batches, whether approved or rejected. |
| 21 CFR 211.188(b)(8) | Labeling Control Records and Label Copies | The batch production and control records are deficient in that they do not include complete labelling control records specimen copy of labelling. |
| 21 CFR 212.20(d) | Determination need for investigation | When errors occurred or a production batch or any component of the batch, failed to meet specifications, you did not determine the need for an investigation, conduct an investigation, and take appropriate corrective actions when necessary. |
| FDCA 501(a)(2)(A) | Cleanliness, ISO-classified areas | The ISO 5 classified aseptic processing areas had difficult to clean particle-generating, visibly dirty equipment or surface. |
| 21 CFR 211.28(a) | Protective Apparel Not Worn | Protective apparel is not worn as necessary to protect drug products from contamination. |
| 21 CFR 211.122(d) | Label storage access limited to authorized personnel | Access to the storage area for labels and labelling materials is not limited to authorized personnel. |
| 21 CFR 211.166(b) | Adequate number of batches on stability | An adequate number of batches of each drug product are not tested nor are records of such data maintained to determine an appropriate expiration date. |
| 21 CFR 211.194(c) | Testing and standardization of standards | Laboratory records do not include complete records of any testing and standardization of laboratory reference standards, reagents, standard solutions. |
| 21 CFR 211.170(b) | Reserve samples identified, representative, stored | Reserve drug product samples are not appropriately identified representative of each lot or batch of drug product retained and stored under conditions consistent with product labelling. |
| 21 CFR 211.194(a)(8) | Second person sign off | Laboratory records do not include the initials or signature of a second person showing that the original records have been reviewed for accuracy, completeness, compliance with established standards. |
| 21 CFR 211.110(b) | In-process conformity – examination, sample testing | Your examination and testing of samples did not assure that the drug product and in-process material conformed to specifications. |
| 21 CFR 211.42(a) | Buildings of Suitable Size, Construction, Location | Buildings used in the manufacture, processing, packing, or holding of a drug product do not have the suitable size,construction,location to facilitate cleaning, maintenance, and proper operations. |
| 21 CFR 211.125(f) | Procedures Written and Followed | Procedures describing in sufficient detail the controls employed for the issuance of labelling are not written, followed. |
| 21 CFR 211.84(c)(4) | Top/Middle/Bottom container sampling | Sampling procedures are deficient regarding sampling components from the top, middle, and bottom of container. |
| 21 CFR 211.186(a) | Written procedures followed | Procedures for the preparation of master production and control records are not described in a written procedure followed. |
| 21 CFR 211.186(b)(9) | Manufacturing Instructions and Specifications | The master production and control records are deficient in that they do not include complete manufacturing, control, instructions, sampling, testing, procedures, specifications, special notations, precautions. |
| 21 CFR 211.186(b)(7) | Theoretical yield statement including percentages | Master production and control records lack a statement of theoretical yield including the maximum and minimum percentages of theoretical yield beyond which investigation is required. |
| 21 CFR 211.42(b) | Adequate space lacking to prevent mix-ups and contamination | The building lacks adequate space for the orderly placement of equipment and materials to prevent mix-ups between, different components ,drug product containers ,closures ,labelling ,in-process materials, drug products and to prevent contamination. |
| FDCA 501(a)(2)(A) | Non-microbial contamination, production area | Non-microbial contamination was observed in your production area. |
| FDCA 501(a)(2)(A) | Disinfecting and cleaning agents, ISO 5 area | Disinfecting agents and cleaning pads, cleaning wipes used in the ISO 5 classified aseptic processing areas were not sterile. |
| 21 CFR 212.30(b) | Equipment procedures | You did not implement procedures document your activities in accordance with your procedures to ensure that all equipment is cleaned suitable for its intended purposes properly installed, maintained, and capable of repeatedly producing valid results that could reasonably be expected to adversely affect the identity, strength, quality, or purity of a drug, or give erroneous or invalid test results when improperly used or maintained. |
| 21 CFR 211.22(a) | Contract drug products–lack of responsibility | The quality control unit lacks responsibility for approving or rejecting drug products manufactured, processed, and packed held under contract by another company. |
| 21 CFR 211.25(c) | Inadequate number of personnel | The number of qualified personnel is inadequate to perform, supervise the manufacture, processing, packing, holding of each drug product. |
| 21 CFR 211.68(b) | Backup file not maintained | Failure to maintain a backup file of data entered into the computer or related system. |
| 21 CFR 211.165(d) | Acceptance criteria for sampling & testing | Acceptance criteria for the sampling and testing conducted by the quality control unit is not adequate to assure that batches of drug products meet each appropriate specification, appropriate statistical quality control criteria as a condition for their approval and release. |
| 21 CFR 211.68(b) | Written record not kept of program and validation data | A written record of the program along with appropriate validation data has not been maintained in situations where backup data is eliminated by computerization or other automated processes. |
| 21 CFR 211.160(b)(4) | Instruments, apparatus, et. al. not meeting specs | The use of instruments apparatus gauges recording devices not meeting established specifications was observed. |
| 21 CFR 211.170(b)(1) | Retention time of reserve samples, in general | You did not retain reserve samples for drug products for one year after the expiration dates of the drug products. |
| 21 CFR 211.194(a)(2) | Suitability of testing methods verified | The suitability of all testing methods is not verified under actual conditions of use. |
| 21 CFR 212.60(c) | Analytical methods | Your laboratory analytical methods are not suitable for their intended use, sufficiently sensitive, sufficiently specific, sufficiently accurate, and sufficiently reproducible. |
| FDCA 503B(a)(10) | Drug product label, outsourcer facility | The labels of your outsourcing facility’s drug products are deficient. |
| FDCA 501(a)(2)(A) | Highly potent drugs, prevention of cross-contamination | You produced highly potent drugs without providing adequate containment segregation, cleaning of work surfaces, cleaning of utensils, cleaning of personnel to prevent cross-contamination. |
| FDCA 501(a)(2)(A) | Improper gowning, contamination | Personnel donned gowning apparel improperly, in a way that may have caused the gowning apparel to become contaminated. |
| FDCA 501(a)(2)(A) | Personnel habits, contamination | Personnel did not disinfect, change gloves frequently enough to prevent contamination. |
| FDCA 501(a)(2)(A) | Flow of personnel and materials, facility | Your facility was designed and/or operated in a way that permits poor flow of personnel/materials. |
| 21 CFR 211.42(b) | Product flow through building is inadequate | The flow of components drug product containers,closures,labelling,in-process materials, drug products though the building is not designed to prevent contamination. |
| 21 CFR 211.67(b)(5) | Cleaning SOPs/equipment protection | Procedures for the cleaning and maintenance of equipment are deficient regarding the protection of clean equipment from contamination prior to use. |
| 21 CFR 211.130 | Procedures are written, and followed | Procedures designed to assure that correct labels, labelling, packaging materials are used for drug products are not written followed. |
| 21 CFR 211.188(a) | Accurate reproduction | The batch production and control records are deficient in that they are not an accurate reproduction of the appropriate master production or control record checked for accuracy, dated, and signed. |
| 21 CFR 211.188(b)(11) | Identification of Persons Performing Significant Steps | The batch production and control records are deficient in that they do not include identification of persons performing, supervising, and checking each significant step in the operation. |
| 21 CFR 211.65(a) | Equipment construction – reactive surfaces | Equipment surfaces that contact components, in-process materials, drug products are reactive, additive or absorptive so as to alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements. |
| 21 CFR 211.84(d)(2) | Component identification test | Specific identification tests are not conducted on components that have been accepted based on the supplier’s report of analysis. |
| 21 CFR 211.105(a) | Identification of containers, lines, equipment | All compounding and storage containers processing lines, major equipment used during the production of a batch of drug product is not properly identified at all times to indicate contents, the phase of processing of the batch. |
| 21 CFR 211.160(b)(2) | Acceptance of in-process materials | Determinations of conformance to appropriate written specifications for acceptance are not made deficient for in-process materials. |
| 21 CFR 211.160(b)(3) | Drug product sample | Drug product samples are not representative of the entire batch properly identified. |
| 21 CFR 211.84(d)(6) | Microbiological Contamination Exam | Each lot of a component drug product container, closure that is liable to microbiological contamination that is objectionable in view of its intended use is not subjected to microbiological tests before use. |
| 21 CFR 211.150(b) | Recall facilitation | A system by which the distribution of each lot of drug product can be readily determined to facilitate its recall if necessary, has not been established. |
| 21 CFR 211.188(b)(8) | Labeling control records including specimens or copies | Batch production and control records do not include complete labelling control records, including specimens or copies of all labeling used for each batch of drug product produced. |
| FDCA 501(a)(2)(A) | Ceiling tiles, cleanroom | Unsealed, loose ceiling tiles were observed in your clean room. |
| 21 CFR 211.42(c)(1) | Incoming material area | Separate or defined areas to prevent contamination or mix-ups are deficient regarding operations related to the receipt, identification, storage, and withholding from use of components, drug product containers, closures, labelling, pending sampling, testing, or examination by the quality control unit before release for manufacturing or packaging. |
| 21 CFR 211.122(a) | Written procedures describing in detail | There is a lack of written procedures describing in sufficient detail the receipt,identification,storage,handling,sampling,examination,testing of labeling and packaging materials. |
| 21 CFR 211.122(d) | Labels and labeling stored separately | Labels and other labeling materials are not stored separately with suitable identification for each different drug product, strength, dosage form or quantity of contents. |
| 21 CFR 211.87 | Retest of approved components/containers/closures | Approved components, drug product containers, closures are not retested or re-examined as appropriate for identity, strength, quality and purity after storage for long periods exposure to conditions that might have an adverse effect with subsequent approval or rejection by the quality control unit. |
| 21 CFR 211.165(c) | Sampling and testing plans not described | Sampling and testing plans for drug products are not described in written procedures which include the method of sampling number of units per batch to be tested. |
| 21 CFR 211.166(a)(1) | Sample size – test intervals | The written stability program for drug products does not include sample size, test intervals based on statistical criteria for each attribute examined to assure valid estimates of stability. |
| 21 CFR 211.182 | Personnel dating/signing equipment log | The persons performing double-checking the cleaning and maintenance are not dating signing or initialing the equipment cleaning and use log. |
| 21 CFR 211.56(c) | Written procedures lacking for use of pesticides etc. | Written procedures are lacking for the use of rodenticides,insecticides,fungicides,fumigating agents, cleaning and sanitizing agents] designed to prevent the contamination of equipment,components,drug product containers,closures,packaging, labelling materials, drug products. |
| 21 CFR 211.170(a) | Active ingredient retained sample kept | A sample which is representative of each lot in each shipment of each active ingredient is not appropriately identified, retained. |
| 21 CFR 211.110(b) | In-process materials specifications testing | Examination and testing of samples is not done to assure that in-process materials conform to specifications. |
| 21 CFR 211.160(b)(3) | Drug products-sampling procedures/specifications | Laboratory controls do not include a determination of conformance to written descriptions of sampling procedures appropriate specifications for drug products. |
| 21 CFR 211.170(b) | Reserve drug product sample quantity – all tests | The reserve sample of drug product does not consist of at least twice the quantity necessary to perform all the required tests of drug product. |
| 21 CFR 211.198(b) | Written complaint record to be maintained at facility | A written record of each complaint is not maintained in a file designated for drug product complaints at the facility where the drug product was manufactured, processed or packed at a facility other than the facility in which the drug product was manufactured, processed or packed provided the written records are readily available for inspection at that other facility]. |
| 21 CFR 212.60(a) | Testing procedures | Each laboratory used to conduct testing of components, in-process materials, finished drug products does not have follow written procedures for the conduct of each test for the documentation of the results. |
| FDCA 501(a)(2)(A) | Beta-lactam drugs, inadequate sanitation | You produced beta-lactam drugs without providing adequate containment, segregation, cleaning of work surfaces, cleaning of utensils, cleaning of personnel to prevent cross-contamination. |
| FDCA 501(a)(2)(A) | Inadequate HEPA filter, Manufacturing area | You had inadequate HEPA filter coverage,airflow over the area to which product was exposed. |
| FDCA 501(a)(2)(A) | Disinfectant contact time | Disinfectant contact time (also known as “dwell time”) and coverage of the item being disinfected were insufficient to achieve adequate levels of disinfection. |
| 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,labeling before disposition. |
| 21 CFR 211.42(c)(5) | Mfg / Processing Operations Area | Separate or defined areas to prevent contamination or mix-ups are deficient regarding the manufacturing and processing operations. |
| 21 CFR 211.130(a) | Prevention of cross contamination, mix-ups | There is insufficient physical or spatial separation from operations and other drug products to prevent mix-ups and cross-contamination. |
| 21 CFR 211.84(b) | Representative Samples Criteria | The number of containers to be sampled, amount of material taken from each container is not based upon appropriate criteria. |
| 21 CFR 211.94(c) | Containers & Closures Clean, Sterilized, Pyrogen-free | Drug product containers, closures were not clean, sterilized and processed to remove pyrogenic properties to assure that they are suitable for their intended use. |
| 21 CFR 211.184(d) | Labeling: documentation of exam and review | There is no documentation of the examination and review of labels and labeling for conformity with established specifications the assigning of a lot or control number. |
| 21 CFR 211.186(a) | Signature and checking of records — 2 persons | The master production and control records for each batch size of drug product are not prepared, dated, and signed by one person with a full handwritten signature independently checked, dated, and signed by a second person. |
| 21 CFR 211.194(a)(2) | Laboratory Test Method Verification | Verification of the suitability of the testing methods is deficient in that they are not performed under actual conditions of use documented on the laboratory records. |
| 21 CFR 211.52 | Washing and toilet facilities are deficient | Washing and toilet facilities lack hot and cold water ,soap or detergent ,air driers or single-service towels ,cleanliness. |
| 21 CFR 211.56(b) | Written sanitation procedures lacking | There is a lack of written procedures assigning responsibility providing cleaning schedules, describing in sufficient detail the methods, equipment and materials to be used for sanitation. |
| 21 CFR 211.188(a) | Accurate reproduction included | Batch production and control records for each batch of drug product produced do not include an accurate reproduction of the appropriate master production or control record which was checked for accuracy, dated and signed. |
| 21 CFR 211.194(a)(1) | Sample identification and other information | Laboratory records do not include a description of the sample received for testing, the source or location from where the sample was obtained, the quantity of the sample ,the lot number or other distinctive code of the sample, the date the sample was taken, the date the sample was received for testing. |
| FDCA 501(a)(2)(A) | Inadequate sporicidal agents, cleanroom and ISO 5 area | The use of sporicidal agents in the clean rooms ISO 5 classified aseptic processing area was inadequate infrequent. |
| 21 CFR 211.110(b) | In-process specification, invalid | Your in-process specifications for sampling and testing of in-process materials and drug products were inconsistent with drug product final specifications were not derived from previous acceptable process average and process variability estimates were not determined by the application of suitable statistical procedures. |
| 21 CFR 211.25(b) | Supervisor Training/Education/Experience | Individuals responsible for supervising the manufacture,processing,packing,holding of a drug product lack the education ,training ,experience to perform their assigned functions in such a manner as to assure the drug product has the safety, identity, strength, quality and purity that it purports or is represented to possess. |
| 21 CFR 211.28(b) | Habits of good sanitation & health | Production personnel were not practicing good sanitation and health habits. |
| 21 CFR 211.67(b)(6) | Cleaning SOP/inspection | Procedures for the cleaning and maintenance of equipment are deficient regarding inspection of the equipment for cleanliness immediately before use. |
| 21 CFR 211.42(d) | Penicillin processing area not kept separate | The operations relating to the manufacture processing, packing of penicillin are not performed in facilities separate from those used for other drug products for human use. |
| 21 CFR 211.105(b) | Distinctive ID or code not recorded in batch record | The batch records do not record the distinctive identification number code, name of equipment to identify major equipment to show the specific equipment used in the manufacture of a batch of a drug product. |
| 21 CFR 211.42(c)(7) | Quarantined Drug Products Area | Separate or defined areas to prevent contamination or mix-ups are deficient regarding operations related to the quarantine storage of drug products prior to release. |
| 21 CFR 211.42(c)(9) | Control / Lab Operations Area | Separate or defined areas to prevent contamination or mix-ups are deficient regarding laboratory controls and operations. |
| 21 CFR 211.42(c)(10)(ii) | Temperature / Humidity Controls | Processing areas are deficient regarding temperature, humidity controls. |
| 21 CFR 211.130(e) | Packaging line inspection before use | Inspection of the packaging,labeling facilities immediately before use is not done to assure that all drug products have been removed from previous operations. |
| 21 CFR 211.142(a) | Quarantine – actual practice | Drug products are not quarantined before being released by the quality unit. |
| 21 CFR 211.82(b) | Quarantine Storage of Components | Incoming components, drug product containers ,closures are not stored under quarantine until they have been tested or examined, as appropriate, and released. |
| 21 CFR 211.180(b) | Record maintenance 1 year | All records of production, control, distribution, components, drug product containers, closures, labeling] associated with a batch of drug product were not maintained at least one (1) year after the expiration date. |
| 21 CFR 211.184(e) | Records of disposition of rejected material | Records do not include the disposition of rejected components drug product containers,closures ,labeling. |
| 21 CFR 211.188(b)(10) | Documentation of Sampling Performed | The batch production and control records are deficient in that they do not include documentation of sampling performed. |
| 21 CFR 211.194(a)(6) | Comparison of Test Results to Specifications | Laboratory records are deficient in that they do not include a statement of the results of tests and how they compare to the established specifications, standards. |
| 21 CFR 211.194(a)(7) | Identification of Person Performing the Testing | Laboratory records are deficient in that they do not include the initials signature of the person performing the tests and the dates the tests were performed. |
| 21 CFR 211.44 | Adequate lighting not provided | Adequate lighting is not provided in all areas. |
| 21 CFR 211.46(a) | Adequate ventilation not provided | Adequate ventilation is not provided. |
| 21 CFR 211.46(c) | Air recirculation of dust from production areas | Air is recirculated to production areas, without adequate measures to control recirculation of dust. |
| 21 CFR 211.110(b) | In-process materials specifications | In-process specifications are not consistent with drug product final specifications ,derived from previous acceptable process average and process variability estimates where possible determined by the application of suitable statistical procedures where appropriate. |
| 21 CFR 211.110(c) | In-process materials characteristics testing | In-process materials are not tested for [identity] [strength] [quality] [purity] and approved or rejected by the quality control unit [during the production process] [after storage for long periods]. Specifically, *** |
| 21 CFR 211.110(d) | Rejected in-process materials not quarantined | Rejected in-process materials are not identified controlled under a quarantine system to prevent their use in manufacturing or processing operations for which they are unsuitable. |
| 21 CFR 211.160(b)(4) | Written calibration procedures | Written calibration procedures for instruments, apparatus, gauges, and recording devices are deficient in that they do not include specific directions, schedules, and limits for accuracy and precision provisions for remedial action if limits are not met. |
| 21 CFR 211.160(b)(4) | Test devices not meeting specifications | Test devices are deficient in that instruments, apparatus, gauges, recording devices not meeting established specifications are used. |
| 21 CFR 211.204 | Returned drug procedures in writing and followed | Procedures describing the holding, testing, reprocessing of returned drug products are not in writing, followed. |
| 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 211.110(a) | Control procedures fail to include the following | Control procedures fail to include tablet or capsule weight variation, disintegration time, adequacy of mixing to assure uniformity and homogeneity, dissolution time and rate, clarity, completeness or pH of solutions. |
| 21 CFR 211.150 | Written distribution procedure | Written distribution procedures are not established and followed. |
| 21 CFR 211.165(d) | Acceptance/Rejection Levels | The statistical quality control criteria fail to include appropriate acceptance levels, rejection levels. |
| 21 CFR 211.188(b)(11) | Identification of persons involved, each significant step | Batch production and control records do not include the identification of the persons performing, directly supervising, checking each significant step in the operation, for each batch of drug product produced. |
| 21 CFR 212.10 | Personnel not qualified | You lack a sufficient number of personnel with the necessary education, background ,training, experience to perform their assigned functions. |
| 21 CFR 212.50(a) | Written control procedures | You did not have written production and process control procedures to ensure document that all key process parameters are controlled any deviations from the procedures are justified. |
| 21 CFR 212.60(e) | Equipment | All equipment used to perform the testing is not suitable for its intended purposes capable of producing valid results. |
| 21 CFR 212.60(g)(3) | Complete record of all laboratory test data | Laboratory test records did not contain a complete record of all data obtained in the course of each test, including the date and time the test was conducted all graphs, charts, and spectra from laboratory instrumentation, properly identified to show the specific component, in-process material, or drug product for each lot tested. |
| 21 CFR 212.60(g)(5) | Initials, signature, date | Laboratory test records did not contain the initials or signature of the person performing the test. |
| 21 CFR 212.71(c) | Correction of problems | You did not take appropriate action to correct any identified problems to prevent recurrence of a non-conforming product or other quality problem. |
| FDCA 501(a)(2)(A) | Disruption of airflow from personnel movement | Personnel moved rapidly in the vicinity of open sterile units, instruments, which disrupted the airflow and increased the risk of bringing lesser quality air into the ISO 5 classified aseptic processing area. |
| FDCA 501(a)(2)(A) | Non-sterilized and non-depyrogenated, sterile drug | [Non-sterilized] [Non-depyrogenated] equipment was used in sterile drug production. Specifically, *** |
| 21 CFR 211.186(a) | Master production and control records, procedure | The preparation of your master production and control records was not [described in a written procedure] [followed in accordance with your written procedure]. Specifically, *** |
| 21 CFR 211.28(c) | Unauthorized Personnel in Limited Access Areas | Unauthorized personnel have access to enter areas of the buildings and facilities designated as limited access areas. Specifically, *** |
| 21 CFR 211.101(d) | Component addition checked by 2nd person | Each component is not added to a batch by one person and verified by a second person. Specifically, *** |
| 21 CFR 211.42(c)(3) | Released Material Area | Separate or defined areas to prevent contamination or mix-ups are deficient regarding operations related to the storage of released [components] [drug product containers] [closures] [labeling]. Specifically, *** |
| 21 CFR 211.42(c)(4) | In-Process Material Area | Separate or defined areas to prevent contamination or mix-ups are deficient regarding operations related to the storage of in-process materials. Specifically, *** |
| 21 CFR 211.42(c)(8) | Released Drug Products Area | Separate or defined areas to prevent contamination or mix-ups are deficient regarding operations related to the storage of drug products after release. Specifically,*** |
| 21 CFR 211.111 | Deviations of production time limits | Deviations from production time limits [are not justified] [are not documented] [compromise the quality of the drug product]. Specifically, *** |
| 21 CFR 211.115(a) | Reprocessing procedures not written or followed | Procedures prescribing a system for reprocessing batches to insure that the reprocessed batches will conform with all established standards, specifications, and characteristics are not [written] [followed]. Specifically, *** |
| 21 CFR 211.122(e) | Destruction of obsolete labeling | Obsolete or outdated labels, labeling and packaging materials are not destroyed. Specifically, *** |
| 21 CFR 211.125(b) | Examination of issued labels | Labeling materials issued for a batch were not carefully examined for identity and conformity to the labeling specified in the master or batch production records. Specifically, *** |
| 21 CFR 211.125(c) | Label reconciliation discrepancies evaluation/investigation | Discrepancies found outside preset limits when reconciling the quantities of labeling issued, used and returned, were not [evaluated] [investigated]. Specifically, *** |
| 21 CFR 211.130(b) | Unlabeled filled containers controls | Filled drug product containers which are set aside and held in an unlabeled condition are not [identified] [handled] to preclude mislabeling of individual containers, lots or portions of lots. Specifically, *** |
| 21 CFR 211.130(d) | Examination of packaging and labeling | Examination of packaging and labeling materials for suitability and correctness before packaging operations is [not performed] [not documented in the batch production records]. Specifically, *** |
| 21 CFR 211.82(a) | Examination on receipt, before acceptance | Each container or grouping of containers of [components] [drug product containers] [closures] is not examined visually upon receipt and before acceptance for [appropriate labeling as to contents] [container damage] [broken seals] [contamination]. Specifically, *** |
| 21 CFR 211.84(b) | Representative Samples | Representative samples are not taken of each shipment of each lot of [components] [drug product containers] [closures] for testing or examination. Specifically, *** |
| 21 CFR 211.84(c)(2) | Appropriate Opening of Component Containers | The containers of components, or drug product containers or closures which are sampled are not opened in a manner to prevent [contamination of their contents] [contamination of other components] [contamination of other drug product containers] [contamination of other closures]. Specifically, *** |
| 21 CFR 211.84(d)(3) | Container/Closure Written Test Procedure | Drug product container and closure test procedures are deficient in that [containers] [closures] are not tested for conformance in accordance with appropriate written procedures. Specifically, *** |
| 21 CFR 211.94(b) | Protection from external factors | Container closure systems do not provide adequate protection against foreseeable external factors in storage and use that can cause deterioration or contamination of the drug product. Specifically, *** |
| 21 CFR 211.180(b) | Record maintenance 3 years (exempt OTC drugs) | Records for all [production] [control] [distribution] [components] [drug product containers] [closures] [labeling] associated with a batch of OTC drug product exempt from expiration dating were not maintained for 3 years after distribution of the last lot of drug product incorporating the component or using the container, closure, or labeling. Specifically, *** |
| 21 CFR 211.167(a) | Sterility/pyrogens – test methods written, followed | Test procedures relative to appropriate laboratory testing for [sterility] [pyrogens] are not [written] [followed]. Specifically, *** |
| 21 CFR 211.180(e)(2) | Review of problem drugs | The procedures for the annual quality standards record evaluation are deficient in that they do not address a review of [complaint] [recall] [returned drug product] [salvaged drug product] [investigation] records for each drug product. Specifically, *** |
| 21 CFR 211.182 | Specific information required in individual logs | Individual equipment logs do not show [time] [date] [product] [lot number of each batch processed]. Specifically, *** |
| 21 CFR 211.182 | Chronological Order of Equipment Log Entries | The entries in the equipment cleaning and use logs are not in chronological order. Specifically, *** |
| 21 CFR 211.188(b)(2) | Identification of Equipment and Lines | The batch production and control records are deficient in that they do not include the identity of major [equipment] [lines] used. Specifically, *** |
| 21 CFR 211.188(b)(3) | Identification of Components and In-Process Materials | The batch production and control records are deficient in that they do not include specific identification of each [batch of component] [in-process material] used. Specifically, *** |
| 21 CFR 211.188(b)(4) | Weights and Measures of Components Used | The batch production and control records are deficient in that they do not include [weights] [measures] of components used in the process. Specifically, *** |
| 21 CFR 211.188(b)(6) | Documentation of Packaging and Labeling Area Inspections | The batch production and control records are deficient in that they do not include documentation of the inspection of the [packaging] [labeling] area before and after use. Specifically, *** |
| 21 CFR 211.188(b)(7) | Documentation of Actual Yield and Theoretical Yield | The batch production and control records are deficient in that they do not include a statement of the [actual yield] [percentage of theoretical yield]. Specifically, *** |
| 21 CFR 211.208 | Salvaging and return to marketplace | Drug products that have been subjected to improper storage conditions were salvaged and returned to the marketplace without further evidence or inspection. Specifically, *** |
| 21 CFR 211.208 | Records for salvaged drug products | Records for salvaged drug products do not include [name] [lot number] [disposition]. Specifically, *** |
| 21 CFR 211.186(b)(3) | Component Name and Code | The master production and control records are deficient in that they do not include a complete list of components designated by [name] [code] sufficiently specific to indicate any special characteristic. Specifically, *** |
| 21 CFR 211.186(b)(7) | Theoretical Yield and Percentages | The master production and control records are deficient in that they do not include a statement of theoretical yield and [minimum] [maximum] [yield percentages]. Specifically, *** |
| 21 CFR 211.194(a)(3) | Statement of Sample Weights and Measures | Laboratory records are deficient in that they do not include a statement of the [weight] [measure] of the sample used for testing. Specifically, *** |
| 21 CFR 211.194(a)(5) | Testing Calculations | Laboratory records are deficient in that they do not include all calculations performed during testing. Specifically, *** |
| 21 CFR 211.194(a)(8) | Identification of Person Performing Review of Lab Records | Laboratory records are deficient in that they do not include the [initials] [signature] of the second person reviewing the record for accuracy. Specifically, *** |
| 21 CFR 211.198(b) | Complaint File Location | Complaint procedures are deficient in that written complaint files are not maintained at the manufacturing site nor were they readily available from their off-site location. Specifically, *** |
| 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] [follow-up]. Specifically, *** |
| 21 CFR 211.46(c) | Air filtration system lacking in production area | The production area air supply lacks an appropriate air filtration system. Specifically, *** |
| 21 CFR 211.48(a) | Plumbing System Defects | The plumbing system contains defects that could contribute to the contamination of drug products. Specifically, *** |
| 21 CFR 211.48(b) | Drains–Size, Back-siphonage Prevention | Drains are not [of adequate size] [provided with an air break or other mechanical device to prevent back-siphonage where connected directly with a sewer]. Specifically, *** |
| 21 CFR 211.52 | Washing and toilet facilities not provided and accessible | Washing and toilet facilities are not [provided] [easily accessible to working areas]. Specifically, *** |
| 21 CFR 211.84(c)(4) | Composite sample top/middle/bottom | Sampling procedures are deficient regarding compositing for testing of samples collected from the top, middle, and bottom of the component container. Specifically, *** |
| 21 CFR 211.89 | Quarantine of Rejected Components et. al. | Rejected [components] [drug product containers] [closures] are not controlled under a quarantine system designed to prevent their use in manufacturing or processing operations for which they are unsuitable. Specifically, *** |
| 21 CFR 211.101(b) | Measured components for manufacturing | Components for drug product manufacturing are not [weighed] [measured] [subdivided as appropriate]. Specifically, *** |
| 21 CFR 211.101(c)(1) | Q.C. release check by second individual | Component containers dispensed to manufacturing are deficiently examined by a second person in that the component is not released by the quality control unit. Specifically, *** |
| 21 CFR 211.101(d) | Verification of component addition | Each component is not added to the batch by one person and verified by a second person.. Specifically, *** |
| 21 CFR 211.110(a)(1) | Tablet or capsule weight variation | The in-process control procedures were deficient in that it did not include an examination of [tablet] [capsule] weight variation. Specifically, *** |
| 21 CFR 211.160(b)(1) | Specification description of sample/testing | The specifications for components, drug product containers or closures and labeling are deficient in that they do not include a description of the [sampling plan] [testing procedures]. Specifically, *** |
| 21 CFR 211.160(b)(2) | Sampling/testing of in-process materials | The specifications for in-process materials are deficient in that they do not include a description of the [sampling plan] [testing procedures] for in-process materials. Specifically, *** |
| 21 CFR 211.160(b)(3) | Sampling/testing of drug products | The specifications for drug products are deficient in that they do not include a description of the [sampling plan] [testing procedures] for drug products. Specifically, *** |
| 21 CFR 211.170(b) | Drug product reserve containers | Drug product reserve samples are not stored in [the same immediate container-closure system as the marketed product] [an immediate container-closure system that has essentially the same characteristics as the marketed product]. Specifically, *** |
| 21 CFR 211.170(b) | Investigation of reserve sample deterioration | Evidence of reserve drug product sample deterioration was not [investigated] [recorded and maintained with other stability data]. Specifically, *** |
| 21 CFR 211.170(b)(1) | Reserve sample retention time | The retention period for drug product reserve samples (except those described in 211.170(b)(2) and (3)) is deficient in that they are not retained for one year after the expiration date of the drug product. Specifically, *** |
| 21 CFR 211.56(b) | Written sanitation procedures not followed | Written procedures for sanitation are not followed. Specifically, *** |
| 21 CFR 211.84(d)(3) | Certificates of Testing (Containers, Closures) | Certificates of testing of [containers] [closures] are accepted in lieu of testing without [a visual identification] [establishing the reliability of the supplier’s test results through appropriate validation of the test results at appropriate intervals]. Specifically, *** |
| 21 CFR 211.101(d) | Component release checked by 2nd person | Each container of component dispensed to manufacturing is not examined by a second person to assure that [the component was released by the quality control unit] [the weight or measure is correct as stated in the batch records] [the containers are properly identified]. Specifically, *** |
| 21 CFR 211.115(a) | Reprocessing procedures lack steps to be taken | Reprocessing procedures lack the steps to be taken to insure that reprocessed batches will conform with all established standards, specifications, and characteristics. Specifically, *** |
| 21 CFR 211.130(e) | Packaging line inspection documentation | Results of inspection of packaging and labeling facilities are not documented in the batch production records. Specifically, *** |
| 21 CFR 211.160(b)(2) | In process materials – conformance to written specs | Laboratory controls do not include a determination of conformance to written specifications for in-process materials. Specifically, *** |
| 21 CFR 211.166(b) | Tentative expiration date | Where data from accelerated studies was used to project a tentative expiration date beyond a date supported by actual shelf life studies, there were no [stability studies] [drug product testing at appropriate intervals] conducted until the tentative expiration date was verified or the appropriate expiration date determined. Specifically, *** |
| 21 CFR 211.176 | Failing to test for penicillin cross-contamination | Non-penicillin drug products were not tested for the presence of penicillin, when a reasonable possibility existed that a non-penicillin drug product has been exposed to a cross-contamination with penicillin. Specifically, *** |
| 21 CFR 211.188(b)(12) | Investigations made into any unexplained discrepancy | Batch production and control records do not include the results of any investigation made into any unexplained discrepancy, whether or not the batch of drug product had already been distributed. Specifically, *** |
| 21 CFR 211.188(b)(4) | Weights and measures of components used | Batch production and control records do not include the weights and measures of components used in the course of processing each batch of drug product produced. Specifically, *** |
| 21 CFR 211.188(b)(3) | Identification of each component or in-process material | Batch production and control records do not include the specific identification of each batch of [component] [in-process material] used for each batch of drug product produced. Specifically, *** |
| 21 CFR 211.188(b)(2) | Identity of major equipment and lines used | Batch production and control records do not include the identity of individual major [equipment] [lines] used for each batch of drug product produced. Specifically, *** |
| 21 CFR 211.188(b)(1) | Dates not included for each significant step | Batch production and control records do not include dates of each significant step in the [manufacture] [processing] [packing] [holding] of the batch for each batch of drug product produced. Specifically, *** |
| 21 CFR 211.198(a) | Complaints reviewed by Quality Control Unit | Written procedures describing the handling of complaints do not include provisions for [review by the quality control unit of any complaint involving the possible failure of a drug product to meet any of its specifications] [a determination as to the need for an investigation of any unexplained discrepancy] [explaining the reasons for the failure of the batch or any of its components to meet specifications]. Specifically, *** |
| 21 CFR 211.194(a)(4) | Data secured in course of each test | Laboratory records do not include a complete record of all data secured in the course of each test, including all [graphs] [charts] [spectra] from laboratory instrumentation, properly identified to show the [specific component] [drug product container] [closure] [in-process material] [lot tested] [drug product tested]. Specifically, *** |
| 21 CFR 310.305(c)(2) | Investigation of serious, unexpected events | Serious, unexpected adverse drug experiences have not been [promptly] investigated. Specifically, *** |
| 21 CFR 314.80(c) | [NDA prod] Fail to submit report in apprvd electronic format | You did not submit adverse drug experience information in electronic format. Specifically, *** |
| 21 CFR 314.80(c)(2) | Interval | Periodic reports of non-alert adverse drug experiences have not been submitted [quarterly for an application which was approved less than three years ago] [yearly for an application which was approved three or more years ago]. Specifically, *** |
| 21 CFR 314.80(c)(2)(ii)(A) | Incomplete periodic safety report | You failed to submit a periodic report containing [a narrative summary and analysis of the ADE information for the reporting interval in the report] [an analysis of the post marketing 15-day Alert reports submitted during the reporting interval] [a history of actions taken since the last report because of adverse drug experiences] [an index with a line listing of your patient identification code and adverse reaction term(s) for all ICSRs you submitted for the reporting interval]. Specifically, *** |
| FDCA 760(b)(1) | Failure of responsible person to report AE (non-RX Drug) | Serious adverse event(s) for a non-prescription drug used in the United States has not been reported to the Secretary of HHS. Specifically, *** |
| FDCA 760(b)(1) | No label copy submitted with AE report (non-Rx drug) | Copies of labels from on or within the retail package of a non-prescription drug did not accompany serious drug event report. Specifically, *** |
| 21 CFR 212.30(c) | Contact surfaces | Your equipment is not [constructed] [maintained] so that surfaces that contact [components] [in-process materials] [PET drugs] are not reactive, additive, or absorptive so as to alter the quality of the PET drugs. Specifically,*** |
| 21 CFR 212.20(c) | Adverse effects of changes made | You did not demonstrate that any change does not adversely affect the [identity] [strength] [quality] [purity] of your PET drug. Specifically,*** |
| 21 CFR 212.40(c) | Each lot identified and tested | Each lot of [components] [containers] [closures] is not [uniquely identified] [tested or examined to determine compliance with your specifications]. Specifically,*** |
| 21 CFR 212.40(c)(2) | Rep.sample – containers/closures | You did not examine a representative sample of each lot of [containers] [closures] for conformity to written specifications. Specifically,*** |
| 21 CFR 212.50(b) | Master Production and Control Records | You did not have master production and control records that document all steps in the PET drug production process. Specifically,*** |
| 21 CFR 212.50(b)(6) | Action limits on radiochemical yield | Your master production and control records did not include a statement of action limits on radiochemical yield. Specifically,*** |
| 21 CFR 212.50(b)(7) | Complete instructions, procedures, specs | Your master production and control records did not include complete [production and control instructions] [sampling and testing procedures] [specifications] [special notations] [precautions to be followed]. Specifically,*** |
| 21 CFR 212.50(c)(4) | Each major production step | Your batch production record does not include each major production step (obtained from the approved appropriate master production and control record). Specifically, *** |
| 21 CFR 212.50(d) | Production area & equipment checks | Your [production area] [equipment in the production area] was not checked to ensure [cleanliness] [suitability] immediately before use. Specifically,*** |
| 21 CFR 212.60(f) | Lab written procedures | Laboratory written procedures are not [established] [followed] to ensure that the lab equipment is routinely [calibrated] [inspected] [checked] [maintained]. Specifically,*** |
| 21 CFR 212.60(g) | Test records complete (general) | Each laboratory used to perform tests related to the production of a PET drug did not keep complete records of all tests performed to ensure compliance with established specifications and standards, including examinations and assays. Specifically,*** |
| 21 CFR 212.70(c) | Conform to specs prior to release | You did not conduct an appropriate laboratory determination to ensure that each batch of a PET drug product conforms to specifications before final release. Specifically, *** |
| 21 CFR 212.70(d)(3) | Final dated signature | You did not [establish] [follow] procedures to ensure that each batch or sub-batch of a PET drug was not given final release until a designated qualified individual authorized the final release by dated signature. Specifically, *** |
| 21 CFR 212.70(e) | When 30 hour rule is exceeded | A sample for sterility testing was held longer than 30 hours, but you did not demonstrate that the longer period did not adversely affect the sample and that the test results obtained were equivalent to test results that would have been obtained if the test had been started within the 30 hour period. Specifically,*** |
| 21 CFR 212.71(a) | Rejection of nonconforming product | You did not reject the batch of a PET drug product that did not conform to specifications. Specifically,*** |
| 21 CFR 212.80(d) | Labeling and product mix-ups | Labeling and packaging operations for PET drug products were not controlled to prevent labeling and product mix-ups. Specifically,*** |
| 21 CFR 212.100(a) | Written complaint procedures | You have not [developed] [followed] written procedures for the receipt and handling of all complaints concerning the quality or purity of, or possible adverse reactions to, a PET drug product. Specifically,*** |
| 21 CFR 212.71(b) | Documentation of Non-Conforming Product Investigation | You did not document [the results of the investigation] [what happened to the rejected PET drug product] for a PET drug product that did not meet specifications. Specifically, *** |
| 21 CFR 361.1(f)(1) | Packaging, labeling – Rx only | The label of a radioactive drug prepared, packaged, distributed, and primarily intended for use in the RDRC research project did not bear the statement “Rx only”. Specifically, *** |
| 21 CFR 361.1(f)(2) | Label – For research use | The label of a radioactive drug prepared, packaged, distributed, and primarily intended for use in the RDRC research project did not bear a statement that the drug is to be administered in compliance with radioactive drug research use. Specifically, *** |
| 21 CFR 361.1(f)(11) | Label – Parenteral drug, sterile | The label of a radioactive parenteral drug prepared, packaged, distributed, and primarily intended for use in the RDRC research project did not bear a statement as to whether the contents are sterile. Specifically, *** |
| 21 CFR 361.1(f)(12) | Label – Inactive ingredient, name | The label of a radioactive drug prepared, packaged, distributed, and primarily intended for use in the RDRC research project and intended for other than oral use did not bear the name of an inactive ingredient. Specifically, *** |
| 21 CFR 314.80(c)(2)(ii)(B) | Late submission of an ICSR | You failed to submit an ICSR for the reporting period [within 30 days of the close of the quarter] [within 60 days of the anniversary date of the approval of the application]. Specifically, *** |
| 21 CFR 314.80(f)(2) | Incomplete ADE information on ICSR | You submitted an ICSR reporting adverse drug experience information that failed to include the [outcome attributed to adverse drug experience] [date of adverse drug experience] [date of ICSR submission] [description of adverse drug experience including a concise medical narrative] [adverse drug experience term(s)] [description of relevant tests including dates and laboratory data] [other relevant patient history including preexisting medical conditions]. Specifically, *** |
| FDCA 501(a)(2)(A) | Vermin, production area | Vermin was observed in your production area. Specifically, *** |
| FDCA 501(a)(2)(A) | Vermin, adjacent area | Vermin was observed in an area immediately adjacent to your production area. Specifically, *** |
| FDCA 501(a)(2)(A) | Inadequate control, construction adjacent to drug production | Your firm produced drugs while construction was underway in an adjacent area without adequate controls to prevent contamination of the production environment and product. Specifically, *** |
| FDCA 501(a)(2)(A) | Personnel in aseptic processing, non-sterile gloves | Personnel engaged in aseptic processing were observed wearing non-sterile gloves. Specifically, *** |
| FDCA 501(a)(2)(A) | Sterile product air exposure | [Inadequately protected] [Un-protected] product intended to be sterile was exposed to lower than ISO 5 classified aseptic processing area quality air. Specifically, *** |
| FDCA 501(a)(2)(A) | Personnel contact on container or closure | Personnel [used a non-sterile tool on] [manually contacted the inner surface of] the container or closure. Specifically, *** |
| FDCA 501(a)(2)(A) | Dust-collecting overhangs, surrounding area of ISO 5 | The [ISO 5 classified aseptic processing areas] [segregated production areas surrounding the ISO 5 classified aseptic processing area] contained dust-collecting overhangs without adequate and frequent cleaning. Specifically, *** |
| FDCA 501(a)(2)(A) | Location, ISO 5 classified area | The ISO 5 classified aseptic processing area was located within a non-classified room (segregated production area). Specifically, *** |
| FDCA 501(a)(2)(A) | Lack of HEPA filter, sterile product area | You did not have a HEPA filter over the area to which sterile product was exposed. Specifically, *** |
| FDCA 501(a)(2)(A) | Unsealed HEPA filter, perimeter | HEPA filters were not sealed around each perimeter to the support frame. Specifically, *** |
| FDCA 501(a)(2)(A) | Inadequate filter, final product sterilization | The filter intended to render final product sterile [was not adequate to accomplish sterilization] [was not pharmaceutical grade]. Specifically, *** |
| FDCA 505-1(e)(2)(A) | Failure to comply with REMS Medication Guide | An application holder did not dispense the Medication Guide, as required by your approved REMS Medication Guide. Specifically, *** |
| FDCA 505-1(f)(3)(B) | Failure to comply with REMS Elements to Assure Safe Use (ETASU) B | An application holder did not [ensure pharmacies that dispense the drug are specially certified] [ensure mechanisms are in place that allow pharmacies the ability to complete the certification process] [maintain a validated, secure database of certified pharmacies] [identify and address non-compliant certified pharmacies], as required by your approved REMS Element to Assure Safe Use (ETASU) B. Specifically, *** |
| FDCA 505-1(f)(4) | Failure to comply with REMS Implementation System | An application holder did not [ensure wholesalers / distributors who distribute the drug are authorized to distribute the drug] [comply with the audit plan and schedule described in the REMS] [identify and address non-compliant authorized wholesalers / distributors] [maintain a Support / Call Center or a REMS Program website] [maintain the drug distribution and dispensing records to ensure restricted distribution], as required by your approved REMS Implementation System. Specifically, *** |
| FDCA 503B(b)(2)(A) | Outsourcing facility, compounded drug report follow up | Your outsourcing facility did not submit a report to FDA identifying the drugs compounded during the previous six month period. Specifically, *** |
