Pharmacy Courses

FDA 483 Database 2021

A List of FDA 483 Observations in FY 2021

1. The responsibilities and procedures applicable to the quality control unit are not [in writing] [fully followed].


2. 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.  


3. 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.

  

4. 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] [labeling] [drug products] conform to appropriate standards of identity, strength, quality and purity.  


5. 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.  


6. 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.

  

7. 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].  


8. Procedures designed to prevent microbiological contamination of drug products purporting to be sterile are not [established] [written] [followed].  


9. Routine [calibration] [inspection] [checking] of [automatic] [mechanical] [electronic] equipment is not performed according to a written program designed to assure proper performance.  


10. 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].  


11. 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.  


12. Aseptic processing areas are deficient regarding the system for monitoring environmental conditions.  


13. Employees engaged in the [manufacture] [processing] [packing] [holding] of a drug product lack the [education] [training] [experience] required to perform their assigned functions.  


14. Written production and process control procedures are not [followed in the execution of production and process control functions] [documented at the time of performance].  


15. 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.   


16. There is no written testing program designed to assess the stability characteristics of drug products. 

 

17. 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.  


18. Buildings used in the [manufacturing] [processing] [packing] [holding] of a drug product are not maintained in a good state of repair.  


19. Procedures designed to prevent objectionable microorganisms in drug products not required to be sterile are not [established] [written] [followed].  


20. The written stability testing program is not followed.  


21. Laboratory records do not include complete data derived from all tests, examinations and assay necessary to assure compliance with established specifications and standards.


22. 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.  


23. 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.  


24. The [accuracy] [sensitivity] [specificity] [reproducibility] of test methods have not been [established] [documented].  


25. 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].  


26. Procedures describing the handling of written and oral complaints related to drug products are [not written or followed] [deficiently written or followed].  


27. 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. 

 

28. 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.  


29. Written records are not [always] made of investigations into [unexplained discrepancies] [the failure of a batch or any of its components to meet specifications].  


30. Aseptic processing areas are deficient regarding the system for cleaning and disinfecting the [room] [equipment] to produce aseptic conditions.  


31. Procedures designed to prevent microbiological contamination of drug products purporting to be sterile did not include [adequate] validation of the [aseptic] [sterilization] process.  


32. Establishment of the reliability of the component supplier's report of analyses is deficient in that the test results are not appropriately validated at appropriate intervals.  


33. 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]. 

 

34. 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].  


35. The quality control unit lacks authority to [review production records to assure that no errors have occurred] [fully investigate errors that have occurred].  


36. GMP training is not conducted [on a continuing basis] [with sufficient frequency] to assure that employees remain familiar with CGMP requirements applicable to them.  


37. Written procedures are lacking which describe in sufficient detail the [receipt] [identification] [storage] [handling] [sampling] [testing] [approval] [rejection] of [components] [drug product containers] [closures].  


38. Established [specifications] [standards] [sampling plans] [test procedures] [laboratory control mechanisms] are not [followed] [documented at the time of performance].  


39. 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]. 

 

40. The quality control unit lacks responsibility to [approve] [reject] all procedures or specifications impacting on the [identity] [strength] [quality] [purity] of drug products.  


41. Input to and output from [the computer] [related systems of formulas] [records or data] are not checked for accuracy.   


42. Time limits are not established when appropriate for the completion of each production phase to assure the quality of the drug product. 

 

43. Strict control is not exercised over labeling issued for use in drug product labeling operations.  


44. 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.

  

45. Drug products are not stored under appropriate conditions of [temperature] [humidity] [light] so that their identity, strength, quality, and purity are not affected.  


46. Procedures describing the handling of all written and oral complaints regarding a drug product are not [established] [written] [followed].  


47. There is no quality control unit.  


48. 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].  


49. 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].  


50. Complaint records are deficient in that they do not include the findings of the [investigation] [follow-up]. 

 

51. 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].  


52. 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].  


53. Non-microbial contamination was observed in your production area.  


54. 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.  


55. Each batch of drug product required to be free of objectionable microorganisms is not tested through appropriate laboratory testing.  


56. The written stability program for drug products does not include [reliable] [meaningful] [specific] test methods.  


57. Drug product production and control records, are not [reviewed] [approved] by the quality control unit to determine compliance with all established, approved written procedures before a batch is released or distributed.  


58. 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]. 


59. Deviations from written production and process control procedures are not [recorded] [justified].  


60. Written procedures have not been developed for the [surveillance] [receipt] [evaluation] [reporting to FDA] of post marketing adverse drug experiences. 


61. The number of qualified personnel is inadequate to [perform] [supervise] the [manufacture] [processing] [packing] [holding] of each drug product. 


62. 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.  


63. The [separate or defined areas] [control systems] necessary to prevent contamination or mix-ups are deficient.  


64. 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.  


65. 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.  


66. Deviations from written [specifications] [standards] [sampling plans] [test procedures] [laboratory mechanisms] are not [recorded] [justified].  


67. 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 labeling]. 

 

68. 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].  


69. The suitability of all testing methods is not verified under actual conditions of use.  


70. 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]. 

 

71. 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.   


72. 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] [take appropriate corrective actions] when necessary.  


73. 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 PET drug, or give erroneous or invalid test results when improperly used or maintained.  


74. Records of the [calibration checks] [inspections] of automatic, mechanical or electronic equipment, including computers or related systems are not maintained.  


75. 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.  


76. Aseptic processing areas are deficient regarding systems for maintaining any equipment used to control the aseptic conditions.   


77. Each lot of [components] [drug product containers] [closures] is not withheld from use until the lot has been sampled, tested, examined, and released by the quality control unit. 

 

78. Failure to reject any lot of [components] [drug product containers] [closures] that did not meet the appropriate written specifications for identity, strength, quality, and purity.  


79. 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].  


80. 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].  


81. Changes to written procedures are not [drafted, reviewed and approved by the appropriate organizational unit] [reviewed and approved by the quality control unit].  


82. 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.  


83. Backup data is not assured as [exact] [complete] [secure from alteration, erasure or loss] through keeping hard copy or alternate systems.  


84. You did not retain reserve samples for drug products for one year after the expiration dates of the drug products.  


85. The building lacks adequate space for the orderly placement of equipment and materials to prevent mix-ups between [different components] [drug product containers] [closures] [labeling] [in-process materials] [drug products] and to prevent contamination.   


86. Your firm lacks adequate production and process controls to ensure the consistent production of a PET drug that meets the applicable standards of identity, strength, quality and purity.


87. You produced hazardous drugs without providing adequate [containment] [segregation] [cleaning of work surfaces] [cleaning of utensils] [cleaning of personnel] to prevent cross-contamination.  


88. Personnel [conducted aseptic manipulations] [placed equipment/supplies] in an area that blocked the movement of first pass air around an open unit, either before or after it was filled with sterile product.

  

89. The use of sporicidal agents in the [cleanrooms] [ISO 5 classified aseptic processing] area was [inadequate] [infrequent].  


90. 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.  


91. The quality control unit lacks the responsibility and authority to [approve] [reject] all [components] [drug product containers] [closures] [in process materials] [packaging material] [labeling] [drug products].  


92. Protective apparel is not worn as necessary to protect drug products from contamination.  


93. Procedures for the cleaning and maintenance of equipment are deficient regarding inspection of the equipment for cleanliness immediately before use.  


94. Records are not kept for the [maintenance] [cleaning] [sanitizing] [inspection] of equipment. 

 

95. 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.  


96. Separate or defined areas to prevent contamination or mix-ups are deficient regarding operations related to the storage of drug products after release.  


97. Aseptic processing areas are deficient in that [floors] [walls] [ceilings] are not smooth and/or hard surfaces that are easily cleanable. 


98. 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].  


99. There is a lack of written procedures describing in sufficient detail the [receipt] [identification] [storage] [handling] [sampling] [examination] [testing] of labeling and packaging materials.  


100. Procedures describing in sufficient detail the controls employed for the issuance of labeling are not [written] [followed]. 


101. Procedures designed to assure that correct [labels] [labeling] [packaging materials] are used for drug products are not [written] [followed].  


102. Drug product expiration dates do not appear on the labeling in the manner prescribed by regulations.

  

103. There was a failure to handle and store [components] [drug product containers] [closures] at all times in a manner to prevent contamination.  


104. Representative samples are not taken of each shipment of each lot of [components] [drug product containers] [closures] for testing or examination.  


105. Drug product component testing is deficient in that at least one specific test to verify the identity of each component is not performed.  


106. Drug products failing to meet established [standards] [specifications] [quality control criteria] are not rejected.  


107. The written stability program for drug products does not describe the storage conditions for samples retained for testing.  


108. Written records of major equipment [cleaning] [maintenance] [use] are not included in individual equipment logs.  


109. Individual equipment logs do not show [time] [date] [product] [lot number of each batch processed].  


110. 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].  


111. Laboratory records do not include complete records of any testing and standardization of laboratory [reference standards] [reagents] [standard solutions].  


112. Specific identification tests are not conducted on components that have been accepted based on the supplier's report of analysis.  


113. 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.  


114. Determinations of conformance to appropriate written specifications for acceptance are [not made] [deficient] for drug products.  


115. Procedures describing the calibration of instruments, apparatus, gauges and recording devices are [not written or followed] [deficiently written or followed].  


116. Written calibration procedures for instruments, apparatus, gauges, and recording devices are deficient in that they do not include specific [directions] [schedules] [limits for accuracy and precision] [provisions for remedial action if limits are not met].  


117. Written procedures are not followed for the [receipt] [identification] [storage] [handling] [sampling] [testing] [approval] [rejection] of [components] [drug product containers] [closures].  


118. Each component is not tested for conformity with all appropriate written specifications for purity, strength, and quality.  


119. 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.  


120. Results of stability testing are not used in determining [appropriate storage conditions] [expiration dates].  


121. Laboratory records do not include [the initials or signature of the person who performs each test] [the date(s) the tests were performed].  


122. Not all quarterly periodic adverse drug experience reports have been submitted within 30 days of the close of the quarter.  


123. Not all annual periodic adverse drug experience reports have been submitted within 60 days of the anniversary date of the approval of the application.  


124. You did not handle and store [components] [containers] [closures] in a manner that prevents [contamination] [mix-ups] [deterioration] and ensures that they are and remain suitable for their intended use.  


125. The labels of your outsourcing facility's drug products are deficient.  


126. You produced highly potent drugs without providing adequate [containment] [segregation] [cleaning of work surfaces] [cleaning of utensils] [cleaning of personnel] to prevent cross-contamination.  


127. Personnel donned gowning apparel improperly, in a way that may have caused the gowning apparel to become contaminated.  


128. Personnel touched equipment or other surfaces located outside of the ISO 5 classified aseptic processing area with gloved hands and then engaged in aseptic processing without changing or sanitizing gloves.  


129. You did not make adequate product evaluation and take remedial action where actionable microbial contamination was found to be present in the ISO 5 classified aseptic processing area during aseptic production.  


130. The ISO 5 classified aseptic processing areas had [difficult to clean] [particle-generating] [visibly dirty] equipment or surface.  


131. [Equipment was] [Materials or supplies were] not disinfected prior to entering the aseptic processing areas.  


132. Disinfectant contact time (also known as "dwell time") and coverage of the item being disinfected were insufficient to achieve adequate levels of disinfection. 


133. 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.  


134. The quality control unit lacks responsibility for approving or rejecting drug products [manufactured] [processed] [packed] [held] under contract by another company.  


135. Adequate lab facilities for testing and approval or rejection of [components] [drug product containers] [closures] [packaging materials] [in-process materials] [drug products] are not available to the quality control unit.  


136. Production personnel were not practicing good sanitation and health habits. 

 

137. Records are not maintained stating the consultant's [name] [address] [qualifications] [type of service provided].  


138. The flow of [components] [drug product containers] [closures] [labeling] [in-process materials] [drug products] through the building is not designed to prevent contamination.  


139. Procedures for the cleaning and maintenance of equipment are deficient regarding maintenance and cleaning schedules, including, where appropriate, sanitizing schedules.  


140. Procedures for the cleaning and maintenance of equipment are deficient regarding the protection of clean equipment from contamination prior to use.  


141. 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] [labeling] pending sampling, testing, or examination by the quality control unit before release for manufacturing or packaging.  


142. Failure to maintain a backup file of data entered into the computer or related system.  


143. 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.  


144. Separate or defined areas to prevent contamination or mix-ups are deficient regarding the manufacturing and processing operations.  


145. Separate or defined areas to prevent contamination or mix-ups are deficient regarding the packaging and labeling operations. 


146. Aseptic processing areas are deficient regarding [temperature] [humidity] controls.  


147. Aseptic processing areas are deficient regarding air supply that is filtered through high-efficiency particulate air filters under positive pressure.  


148. Labels and other labeling materials are not stored separately with suitable identification for each different drug product, strength, dosage form or quantity of contents.  


149. Access to the storage area for labels and labeling materials is not limited to authorized personnel.  


150. Obsolete or outdated labels, labeling and packaging materials are not destroyed.  


151. There is insufficient physical or spatial separation from operations and other drug products to prevent mix-ups and cross-contamination.   


152. The drug product is not identified with a lot or control number that permits the determination of the history of the manufacture and control of the batch.  


153. The distribution system is deficient in that each lot of drug product cannot be readily determined to facilitate its recall if necessary. 


154. 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].  


155. 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.  


156. Component testing is deficient in that each component is not tested for conformity with all appropriate written specifications for purity, strength, and quality. 


157. Drug product container and closure test procedures are deficient in that [containers] [closures] are not tested for conformance in accordance with  appropriate written procedures. 


158. Each lot of a [component] [drug product containers] [closures] liable to objectionable microbiological contamination is deficiently subjected to microbiological tests before use.  


159. Drug product containers or closures are [reactive] [additive] [absorptive] so as to alter the safety, identity, strength, quality, and purity of the drug beyond the official or established requirements.  


160. 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.  


161. The written stability program does not assure testing of the drug product in the same container-closure system as that in which the drug product is marketed.   


162. There is no written assessment of stability of homeopathic drug products based at least on [testing or examination of the drug product for compatibility of the ingredients] [marketing experience with the drug product to indicate that there is no degradation of the product for the normal or expected period of use].  


163. Each batch of drug product purporting to be [sterile] [pyrogen-free] is not laboratory tested to determine conformance to such requirements.  


164. 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.  


165. 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.  


166. The persons [performing] [double-checking] the cleaning and maintenance are not [dating] [signing or initialing] the equipment cleaning and use log.  


167. 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].  


168. 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.  


169. The batch production and control records are deficient in that they do not include [complete labeling control records] [specimen] [copy] of labeling.  


170. The batch production and control records are deficient in that they do not include documentation of sampling performed.  


171. The batch production and control records are deficient in that they do not include documentation of batch investigations performed.  


172. Distribution records do not contain the [name and strength of the drug product] [description of dosage form] [name and address of consignee] [date and quantity shipped] [lot or control number of drug product].  


173. Laboratory records are deficient in that they do not include a [description and identification of the sample received] [quantity] [lot number] [date sample taken] [date sample received for testing].  


174. Laboratory records are deficient in that they do not include a complete record of all data obtained during testing.  


175. Laboratory records are deficient in that they do not include the [initials] [signature] of the second person reviewing the record for accuracy.  


176. Complaint procedures are deficient in that written complaint records are not maintained in a file designated for drug product complaints.  


177. 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.  


178. 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.  


179. The plumbing system contains defects that could contribute to the contamination of drug products. 

 

180. 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].  


181. Washing and toilet facilities lack [hot and cold water] [soap or detergent] [air driers or single-service towels] [cleanliness].  


182. 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.  


183. 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].  


184. The specifications for [components] [drug product containers] [closure] are deficient in that they do not include appropriate retesting requirements.  


185. Determinations of conformance to appropriate written specifications for acceptance are [not made] [deficient] for in-process materials.  


186. The reserve sample of active ingredient does not consist of at least twice the quantity necessary for all tests required to determine whether the active ingredient meets its established specifications.  


187. 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].  


188. 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.  


189. Each lot of [components] [drug product containers] [closures] was not appropriately identified as to its status in terms of being quarantined, approved or rejected.  


190. Containers are not [opened] [sampled] [resealed] in a manner designed to prevent contamination of [their contents] [other components] [other drug product containers or closures].  


191. 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.  


192. Written procedures for the [receipt] [identification] [storage] [handling] [sampling] [examination] [testing] of packaging and labeling materials are not followed.  


193. Written distribution procedures are not [established] [followed].  


194. Procedures describing the warehousing of drug products are not [established] [followed].  


195. Written specifications for laboratory controls do not include a description of the [sampling] [testing] procedures used.  


196. Samples taken of drug products for determination of conformance to written specifications are not [representative] [properly identified].  


197. Written procedures for sampling and testing plans are not followed for each drug product.  

  

198. The batch production and control records do not include a statement of the [actual yield] [percentage of theoretical yield] at appropriate stages of processing for each batch of drug product produced.  


199. 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.  


200. 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.  


201. 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]. 

 

202. Master production and control records lack [complete manufacturing and control instructions] [sampling and testing procedures] [specifications] [special notations] [precautions to be followed].  


203. 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].   


204. Laboratory records do not include a record of all calculations performed in connection with the test.

   

205. Adverse drug experience information obtained or otherwise received from any source was not [promptly] reviewed, including information from [commercial marketing experience] [post marketing clinical investigations] [post marketing epidemiological/surveillance activities] [reports in the scientific literature] [unpublished scientific papers].  


206. Not all adverse drug experiences that are both serious and unexpected have been reported to FDA within 15 calendar days of initial receipt of the information. 

 

207. Individual ADEs which were not reported to FDA in a post marketing 15-day alert have not been included in a periodic safety report.  


208. 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].  


209. An annual report was not submitted [each year] [within 60 days of the anniversary date of U.S. approval of the application] to the FDA division responsible for reviewing the application.   


210. An adverse event report for a nonprescription drug was not submitted to the Secretary of HHS within 15 business days of receipt of the report.  


211. 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. 


212. You did not oversee production operations in a manner to ensure that each PET drug [meets the requirements of the FD&C Act as to safety] [has the identity and strength that it is supposed to have] [meets the quality and purity characteristics that it is supposed to have].  


213. You did not [establish] [follow] written quality assurance procedures.


214. Your written procedures are not adequate to ensure that the [components] [containers] [closures] are suitable for their intended use. 


215. You did not establish appropriate written specifications for the [identity] [quality] [purity] of components.  


216. You did not establish appropriate written specifications for the [identity] [quality] of drug product [containers] [closures].  


217. 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].  


218. Your [production area] [equipment in the production area] was not checked to ensure [cleanliness] [suitability] immediately before use.  


219. You are not able to demonstrate that your process for producing the PET drug [is reproducible] [is capable of producing a drug product that meets its predetermined acceptance criteria]. 


220. Each laboratory used to conduct testing of [components] [in-process materials] [finished PET drug products] does not [have] [follow] written procedures [for the conduct of each test] [for the documentation of the results].  


221. Each laboratory did not have [sampling] [testing] procedures which are designed to ensure that [components] [in-process materials] [PET drug products] conform to appropriate standards including established standards of identity, strength, quality and purity.  


222. Your laboratory analytical methods are not [suitable for their intended use] [sufficiently sensitive] [sufficiently specific] [sufficiently accurate] [sufficiently reproducible].  


223. All equipment used to perform the testing is not [suitable for its intended purposes] [capable of producing valid results].  


224. You did not [establish] [follow] procedures to ensure that each batch or sub-batch of a PET drug product was not given final release until associated laboratory data and documentation were reviewed and PET drug products were demonstrated to meet specifications.  


225. The container labels of your outsourcing facility's drug products are deficient. 


226. 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].  


227. Vermin was observed in your production area.  


228. Vermin was observed in an area immediately adjacent to your production area. 

 

229. Personnel did not [disinfect] [change gloves frequently enough] to prevent contamination.  


230. HEPA filters were not sealed around each perimeter to the support frame.  


231. Disinfecting agents and [cleaning pads] [cleaning wipes] used in the ISO 5 classified aseptic processing areas were not sterile.  


232. Your examination and testing of samples did not assure that the drug product and in-process material conformed to specifications.  


233. Your master production and control records for each drug product were not [prepared, dated, and signed by one person] [independently checked, dated, and signed by a second person].  


234. Your outsourcing facility did not submit a report to FDA identifying the drugs compounded during the previous six month period.  


235. Your outsourcing facility did not submit a report to FDA upon initial registration as an outsourcing facility identifying the drugs compounded during the previous six month period. 


Read also: FDA Inspection Database