A List of FDA 483 Observations in FY 2023
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. Your firm failed to establish [adequate] written procedures for production and process controls designed to assure that the drug products have the identity, strength, purity, and quality that they are purported or 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 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].
6. 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.
7. Procedures designed to prevent microbiological contamination of drug products purporting to be sterile are not [established] [written] [followed].
8. 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.
9. 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.
10. Aseptic processing areas are deficient regarding the system for monitoring environmental conditions.
11. 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.
12. 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.
13. Procedures designed to prevent microbiological contamination of drug products purporting to be sterile did not include [adequate] validation of the [aseptic] [sterilization] process.
14. The [accuracy] [sensitivity] [specificity] [reproducibility] of test methods have not been [established] [documented].
15. 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.
16. Routine [calibration] [inspection] [checking] of [automatic] [mechanical] [electronic] equipment is not performed according to a written program designed to assure proper performance.
17. Established [specifications] [standards] [sampling plans] [test procedures] [laboratory control mechanisms] are not [followed] [documented at the time of performance].
18. Drug products are not stored under appropriate conditions of [temperature] [humidity] [light] so that their identity, strength, quality, and purity are not affected.
19. 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].
20. Aseptic processing areas are deficient regarding the system for cleaning and disinfecting the [room] [equipment] to produce aseptic conditions.
21. Procedures designed to prevent objectionable microorganisms in drug products not required to be sterile are not [established] [written] [followed].
22. Written production and process control procedures are not [followed in the execution of production and process control functions] [documented at the time of performance].
23. 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].
24. There is no written testing program designed to assess the stability characteristics of drug products.
25. 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].
26. 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.
27. Laboratory records do not include complete data derived from all tests, examinations and assay necessary to assure compliance with established specifications and standards.
28. Buildings used in the [manufacturing] [processing] [packing] [holding] of a drug product are not maintained in a good state of repair.
29. There is no quality control unit.
30. The quality control unit lacks authority to [review production records to assure that no errors have occurred] [fully investigate errors that have occurred].
31. 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.
32. Drug product component testing is deficient in that at least one specific test to verify the identity of each component is not performed.
33. Deviations from written production and process control procedures are not [recorded] [justified].
34. 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.
35. The written stability testing program is not followed.
36. 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].
37. Each batch of drug product required to be free of objectionable microorganisms is not tested through appropriate laboratory testing.
38. 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].
39. Employees engaged in the [manufacture] [processing] [packing] [holding] of a drug product lack the [education] [training] [experience] required to perform their assigned functions.
40. 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.
41. The [separate or defined areas] [control systems] necessary to prevent contamination or mix-ups are deficient.
42. Representative samples are not taken of each shipment of each lot of [components] [drug product containers] [closures] for testing or examination.
43. The written stability program for drug products does not include [reliable] [meaningful] [specific] test methods.
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. 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].
46. Written records are not [always] made of investigations into [unexplained discrepancies] [the failure of a batch or any of its components to meet specifications].
47. 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.
48. Component testing is deficient in that each component is not tested for conformity with all appropriate written specifications for purity, strength, and quality.
49. 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].
50. Procedures describing the handling of written and oral complaints related to drug products are [not written or followed] [deficiently written or followed].
51. Deviations from written [specifications] [standards] [sampling plans] [test procedures] [laboratory mechanisms] are not [recorded] [justified].
52. 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].
53. 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].
54. GMP training is not conducted [on a continuing basis] [with sufficient frequency] to assure that employees remain familiar with CGMP requirements applicable to them.
55. Records of the [calibration checks] [inspections] of automatic, mechanical or electronic equipment, including computers or related systems are not maintained.
56. Input to and output from [the computer] [related systems of formulas] [records or data] are not checked for accuracy.
57. 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.
58. Written records of major equipment [cleaning] [maintenance] [use] are not included in individual equipment logs.
59. 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.
60. 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].
61. You produced hazardous drugs without providing adequate [containment] [segregation] [cleaning of work surfaces] [cleaning of utensils] [cleaning of personnel] to prevent cross-contamination.
62. Aseptic processing areas are deficient regarding systems for maintaining any equipment used to control the aseptic conditions.
63. Time limits are not established when appropriate for the completion of each production phase to assure the quality of the drug product.
64. Written procedures are lacking which describe in sufficient detail the [receipt] [identification] [storage] [handling] [sampling] [testing] [approval] [rejection] of [components] [drug product containers] [closures].
65. 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. Specifically, ***
Drug products failing to meet established [standards] [specifications] [quality control criteria] are not rejected.
66. 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].
67. Laboratory records are deficient in that they do not include a complete record of all data obtained during testing.
68. Written procedures are not [drafted, reviewed and approved by the appropriate organizational units] [reviewed and approved by the quality control unit].
69. 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].
70. 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.
71. Backup data is not assured as [exact] [complete] [secure from alteration, erasure or loss] through keeping hard copy or alternate systems.
72. 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.
73. The quality control unit lacks responsibility to [approve] [reject] all procedures or specifications impacting on the [identity] [strength] [quality] [purity] of drug products.
74. There was a failure to handle and store [components] [drug product containers] [closures] at all times in a manner to prevent contamination.
75. 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.
76. Specific identification tests are not conducted on components that have been accepted based on the supplier's report of analysis.
77. Procedures describing the calibration of instruments, apparatus, gauges and recording devices are [not written or followed] [deficiently written or followed].
78. 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.
79. Written procedures are not followed for the [receipt] [identification] [storage] [handling] [sampling] [testing] [approval] [rejection] of [components] [drug product containers] [closures].
80. Results of stability testing are not used in determining [appropriate storage conditions] [expiration dates].
81. 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].
82. Smoke studies [were not] [were inadequately] performed under dynamic conditions.
83. Strict control is not exercised over labeling issued for use in drug product labeling operations.
84. 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].
85. 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.
86. 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.
87. 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.
88. Changes to written procedures are not [drafted, reviewed and approved by the appropriate organizational unit] [reviewed and approved by the quality control unit].
89. 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].
90. Procedures describing the warehousing of drug products are not [established] [followed].
91. Master production and control records lack [complete manufacturing and control instructions] [sampling and testing procedures] [specifications] [special notations] [precautions to be followed].
92. Written procedures have not been developed for the [surveillance] [receipt] [evaluation] [reporting to FDA] of post marketing adverse drug experiences.
93. Non-microbial contamination was observed in your production area.
94. The preparation of your master production and control records was not [described in a written procedure] [followed in accordance with your written procedure].
95. The number of qualified personnel is inadequate to [perform] [supervise] the [manufacture] [processing] [packing] [holding] of each drug product.
96. Procedures for the cleaning and maintenance of equipment are deficient regarding inspection of the equipment for cleanliness immediately before use.
97. Records are not kept for the [maintenance] [cleaning] [sanitizing] [inspection] of equipment.
Failure to maintain a backup file of data entered into the computer or related system.
98. Aseptic processing areas are deficient regarding air supply that is filtered through high-efficiency particulate air filters under positive pressure.
99. 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].
100. 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.
101. The suitability of all testing methods is not verified under actual conditions of use.
102. You did not [establish] [follow] written quality assurance procedures.
103. The ISO 5 classified aseptic processing areas had [difficult to clean] [particle-generating] [visibly dirty] equipment or surface.
104. 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.
105. Procedures for the cleaning and maintenance of equipment are deficient regarding the protection of clean equipment from contamination prior to use.
106. 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.
Separate or defined areas to prevent contamination or mix-ups are deficient regarding the manufacturing and processing operations.
107. Procedures designed to assure that correct [labels] [labeling] [packaging materials] are used for drug products are not [written] [followed].
108. Inspection of the [packaging] [labeling] facilities immediately before use is not done to assure that all drug products have been removed from previous operations.
109. 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.
110. 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.
111. Records fail to include an individual inventory record of each [component] [reconciliation of the use of each component] [drug product container] [drug product closure] with sufficient information to allow determination of any associated batch or lot of drug product.
112. Procedures for the preparation of master production and control records are not [described in a written procedure] [followed].
113. The batch production and control records are deficient in that they do not include identification of persons [performing] [supervising] [checking] each significant step in the operation.
114. Laboratory records do not include complete records of the periodic calibration of laboratory [instruments] [apparatus] [gauges] [recording devices].
115. Complaint records are deficient in that they do not include the findings of the [investigation] [follow-up].
116. The plumbing system contains defects that could contribute to the contamination of drug products.
117. Each component is not tested for conformity with all appropriate written specifications for purity, strength, and quality.
118. Laboratory controls do not include determination of conformance to appropriate written specifications for the acceptance of each lot within each shipment of [components] [drug product containers] [closures] [in-process materials] [labeling] [drug products] used in the manufacture, processing, packing, or holding of drug products.
119. You did not retain reserve samples for drug products for one year after the expiration dates of the drug products.
120. Procedures describing the handling of all written and oral complaints regarding a drug product are not [established] [written] [followed].
121. 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].
122. Adverse drug experience information has not been reported to FDA.
123. Your examination and testing of samples did not assure that the drug product and in-process material conformed to specifications.
124. You used a non-pharmaceutical grade component in the formulation of a drug product.
Personnel were observed conducting aseptic manipulations where the movement of "first air" in the ISO 5 area is blocked or disrupted.
125. The facility design was observed to allow the influx of lesser quality air into a classified area containing higher quality air.
126. Failure to conduct media fills that closely simulate aseptic production operations under the worst-case, most-challenging, and stressful conditions.
127. The quality control unit lacks responsibility for approving or rejecting drug products [manufactured] [processed] [packed] [held] under contract by another company.
128. Production personnel were not practicing good sanitation and health habits.
129. Separate or defined areas to prevent contamination or mix-ups are deficient regarding laboratory controls and operations.
130. Separate or defined areas to prevent contamination or mix-ups are deficient regarding operations related to aseptic processing of drug products.
131. Aseptic processing areas are deficient in that [floors] [walls] [ceilings] are not smooth and/or hard surfaces that are easily cleanable.
132. Reprocessing was performed without the [review] [approval] of the quality control unit.
133. Labeling and packaging materials are not [representatively sampled] [examined] [tested] upon receipt and before use in packaging and labeling of a drug product.
134. Access to the storage area for labels and labeling materials is not limited to authorized personnel.
Procedures describing in sufficient detail the controls employed for the issuance of labeling are not [written] [followed].
135. Inspection of the [packaging] [labeling] facilities is not done after use to assure that materials not suitable for subsequent operations have been removed.
136. The [number of containers to be sampled] [amount of material taken from each container] is not based upon appropriate criteria.
137. 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].
138. The procedures for the annual quality standards record evaluation are deficient in that they do not address a review of a representative number of [approved] [rejected] batches.
139. The batch production and control records are deficient in that they do not include the identity of major [equipment] [lines] used.
140. The batch production and control records are deficient in that they do not include [in-process] [laboratory] control results.
141. The batch production and control records are deficient in that they do not include [complete labeling control records] [specimen] [copy] of labeling.
142. Laboratory records do not include complete records of any testing and standardization of laboratory [reference standards] [reagents] [standard solutions].
143. 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].
144. 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].
145. Laboratory records are deficient in that they do not include the [initials] [signature] of the second person reviewing the record for accuracy.
146. Adequate exhaust systems or other systems to control contaminants are lacking in areas where air contamination occurs during production.
147. Washing and toilet facilities lack [hot and cold water] [soap or detergent] [air driers or single-service towels] [cleanliness].
148. Each component is not added to the batch by one person and verified by a second person.
149. 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].
150. Determinations of conformance to appropriate written specifications for acceptance are deficient in that they are not made for each lot within each shipment of [components] [drug product containers] [closures] [labeling] used in the manufacture, processing, packing or holding of drug products.
151. Each lot of [components] [drug product containers] [closures] was not appropriately identified as to its status in terms of being quarantined, approved or rejected.
152. Written distribution procedures are not [established] [followed].
153. Samples taken to determine conformance to appropriate written specifications for the acceptance of each lot within each shipment of [components] [drug product containers] [closures] [labeling] are not [representative] [adequately identified].
154. Samples taken of drug products for determination of conformance to written specifications are not [representative] [properly identified].
155. The use of [instruments] [apparatus] [gauges] [recording devices] not meeting established specifications was observed.
156. 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.
157. 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].
158. Laboratory records do not include a record of all calculations performed in connection with the test.
159. Laboratory records do not include [the initials or signature of the person who performs each test] [the date(s) the tests were performed].
160. 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.
161. 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.
162. 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.
163. Your laboratory analytical methods are not [suitable for their intended use] [sufficiently sensitive] [sufficiently specific] [sufficiently accurate] [sufficiently reproducible].
164. All equipment used to perform the testing is not [suitable for its intended purposes] [capable of producing valid results].
165. You produced beta-lactam drugs without providing adequate [containment] [segregation] [cleaning of work surfaces] [cleaning of utensils] [cleaning of personnel] to prevent cross-contamination.
166. Personnel donned gowning apparel improperly, in a way that may have caused the gowning apparel to become contaminated.
167. 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.
168. Disinfecting agents and [cleaning pads] [cleaning wipes] used in the ISO 5 classified aseptic processing areas were not sterile.
169. 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].
170. Your outsourcing facility did not submit a report to FDA identifying the drugs compounded during the previous six month period.
171. Personnel performed aseptic manipulations with exposed hair or skin.
172. Use of non-sterile [disinfecting agents] [cleaning pads] [cleaning wipes] in the [ISO 5 area] [classified areas].
173. Use of a sporicidal agent in the facility's [ISO 5 areas] [classified areas] was [lacking] [improper] [infrequent].
174. 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.
175. Protective apparel is not worn as necessary to protect drug products from contamination.
176. The flow of [components] [drug product containers] [closures] [labeling] [in-process materials ] [drug products] through the building is not designed to prevent contamination.
177. Procedures for the cleaning and maintenance of equipment are deficient regarding maintenance and cleaning schedules, including, where appropriate, sanitizing schedules.
178. Procedures for the cleaning and maintenance of equipment are deficient regarding the removal or obliteration of the previous batch identification.
179. 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.
180. Written production and control procedures include batches formulated with the intent to provide less than 100 percent of the labeled or established amount of active ingredient.
181. Each component is not added to a batch by one person and verified by a second person.
182. 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.
183. 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.
184. Separate or defined areas to prevent contamination or mix-ups are deficient regarding operations related to the storage of drug products after release.
185. Aseptic processing areas are deficient regarding [temperature] [humidity] controls.
186. Deviations from production time limits [are not justified] [are not documented] [compromise the quality of the drug product].
187. 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].
188. Labeling and packaging materials not meeting the appropriate written specifications were [approved] [released for use].
189. Labels and other labeling materials are not stored separately with suitable identification for each different drug product, strength, dosage form or quantity of contents.
190. Obsolete or outdated labels, labeling and packaging materials are not destroyed.
191. 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.
192. 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.
Samples of representative units were not [collected] [visually examined] for correct labeling at the completion of finishing operations.
193. Approved [components] [drug product containers] [closures] are not retested or reexamined 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.
194. Each lot in each shipment received was not identified with a distinctive code for each container or grouping of containers for [components] [drug product containers] [closures].
195. Incoming [components] [drug product containers] [closures] are not stored under quarantine until they have been tested or examined, as appropriate, and released.
196. Sampling procedures are deficient regarding sampling components from the top, middle, and bottom of container.
197. Establishment of the reliability of the [container] [closure] supplier's report of analyses is deficient in that the test results are not appropriately validated at appropriate intervals.
198. Drug product [containers] [closures] were not [clean] [sterilized and processed to remove pyrogenic properties] to assure that they are suitable for their intended use.
199. 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.
200. Records associated with drug product [components] [containers] [closures] [labeling] [production] [control] [distribution] and within the retention period for such records, were not made readily available for authorized inspection.
201. The written stability program for drug products does not describe the storage conditions for samples retained for testing.
202. The written stability program does not include testing of drug products for reconstitution [at time of dispensing - as directed in the labeling] [after they are reconstituted].
203. Accelerated stability studies, combined with basic stability information, used to support tentative expiration dates are not supported with ongoing full shelf life studies.
204. The evaluation of the stability of homeopathic drug products is not based on the same container-closure system in which the drug product is being marketed.
205. Each batch of drug product purporting to be [sterile] [pyrogen-free] is not laboratory tested to determine conformance to such requirements.
206. Test procedures relative to appropriate laboratory testing for [sterility] [pyrogens] are not [written] [followed].
207. 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.
208. Individual equipment logs do not show [time] [date] [product] [lot number of each batch processed].
209. The persons [performing] [double-checking] the cleaning and maintenance are not [dating] [signing or initialing] the equipment cleaning and use log.
210. Records do not include the disposition of rejected [components] [drug product containers] [closures] [labeling].
211. 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].
212. The batch production and control records are deficient in that they do not include [weights] [measures] of components used in the process.
213. The batch production and control records are deficient in that they do not include a statement of the [actual yield] [percentage of theoretical yield].
214. The batch production and control records are deficient in that they do not include documentation of sampling performed.
215. The batch production and control records are deficient in that they do not include documentation of batch investigations performed.
216. Drug products that have been subjected to improper storage conditions were salvaged and returned to the marketplace without further evidence or inspection.
217. Salvaging operations on drug products which may have been subjected to improper storage conditions proceeded in the absence of evidence from [laboratory tests and assays to establish that the drug products meet all applicable standards of identity, strength, quality and purity] [inspection of the premises to establish that the drug products and their associated packaging were not subjected to improper storage conditions as a result of a disaster or accident].
218. 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].
219. Laboratory records are deficient in that they do not include all calculations performed during testing.
220. 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].
221. Complaint procedures are deficient in that they do not include provisions that allow for the review to determine if the complaints represent [serious] [unexpected adverse drug experiences] which are required to be reported to FDA.
222. Complaint procedures are deficient in that written complaint records are not maintained in a file designated for drug product complaints.
223. Complaint records are deficient in that they are not maintained at the establishment where the investigation occurred.
224. 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.
225. Air is recirculated to production areas, without adequate measures to control recirculation of dust.
226. There is a failure to supply potable water under continuous positive pressure.
227. 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.
228. 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, labeling materials] [drug products].
229. Sampling procedures are deficient regarding compositing for testing of samples collected from the top, middle, and bottom of the component container.
230. 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.
231. Components for drug product manufacturing are not [weighed] [measured] [subdivided as appropriate].
232. The packaging and labeling operation involving cut labels and relying on visual inspection does not provide for [100-percent examination for correct labeling during or after completion of finishing operations for hand-applied labeling] [examination to be performed by one person and independently verified by a second person].
233. In-process samples are not [representative] [properly identified].
234. Drug product samples are not [representative of the entire batch] [properly identified].
235. Determinations of conformance to appropriate written specifications for acceptance are [not made] [deficient] for drug products.
236. 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].
237. Test devices are deficient in that [instruments] [apparatus] [gauges] [recording devices] not meeting established specifications are used.
238. A sample which is representative of each lot in each shipment of each active ingredient is not [appropriately identified] [retained].
239. Reserve samples of active drug ingredients are deficient in that they are not retained at least one year after the expiration date of the last lot of the drug containing the active drug ingredient.
240. 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].
241. Evidence of reserve drug product sample deterioration was not [investigated] [recorded and maintained with other stability data].
242. 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.
243. Written procedures for sanitation are not followed.
244. 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.
245. Containers are not [opened] [sampled] [resealed] in a manner designed to prevent contamination of [their contents] [other components] [other drug product containers or closures].
246. 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.
247. For components removed from the original containers, the new container fails to be identified with [component name or item code] [receiving or control number] [weight or measure] [batch for which component was dispensed including product name, strength and lot number].
248. Reprocessing procedures lack the steps to be taken to insure that reprocessed batches will conform with all established standards, specifications, and characteristics.
249. Examination and testing of samples is not done to assure that in-process materials conform to specifications.
250. Written procedures for the [receipt] [identification] [storage] [handling] [sampling] [examination] [testing] of packaging and labeling materials are not followed.
251. 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.
252. The statistical quality control criteria fail to include appropriate [acceptance levels] [rejection levels].
253. 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.
254. 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.
255. 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.
256. 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.
257. Written records of investigation of a drug complaint do not include [the findings of the investigation] [the follow-up].
258. 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].
259. 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].
260. 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.
261. Adverse drug experiences that were the subject of post marketing 15-day reports were not [promptly] investigated.
262. Not all annual periodic adverse drug experience reports have been submitted within 60 days of the anniversary date of the approval of the application.
263. 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].
264. A postmarketing 15-day Alert report based upon scientific literature was not accompanied by a copy of the published article.
265. You failed to maintain for a period of 10 years records of all adverse drug experiences known to you, including raw data and any correspondence.
266. An NDA-Field Alert Report was not submitted within three working days of receipt of information concerning [bacteriological contamination] [significant chemical, physical, or other change or deterioration] in a distributed drug product.
267. 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.
268. Written procedures have not been developed for the [surveillance] [receipt] [evaluation] [reporting to FDA] of postmarketing adverse drug experiences.
269. You lack [a sufficient number of] personnel with the necessary [education] [background] [training] [experience] to perform their assigned functions.
270. 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.
271. You did not establish appropriate written specifications for the [identity] [quality] [purity] of components.
272. 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.
273. Your master production and control records did not include a statement of action limits on radiochemical yield.
274. Your master production and control records did not include identification of all major pieces of equipment used in production.
275. Your batch production record did not include the identification of major pieces of equipment used in production of the batch.
276. Your [production area] [equipment in the production area] was not checked to ensure [cleanliness] [suitability] immediately before use.
277. Your process controls did not include control of in-process materials to ensure that the materials are controlled until required tests or other verification activities have been completed or necessary approvals are received and documented.
278. 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.
279. You did not establish specifications for each PET drug product, including criteria for determining [identity] [strength] [quality] [purity] [sterility] [pyrogens].
280. You implemented a new test procedure in a specification, but you did not first [establish] [document] the [accuracy] [sensitivity] [specificity] [reproducibility] of the procedure.
281. You did not reject the batch of a PET drug product that did not conform to specifications.
282. You did not take [appropriate] action to correct any identified problems to prevent recurrence of a nonconforming product or other quality problem.
283. Labeling and packaging operations for PET drug products were not controlled to prevent labeling and product mix-ups.
284. 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.
285. Your complaint procedures do not include [review by a designated person of any complaint involving the possible failure of a PET drug product to meet any of its specifications] [an investigation to determine the cause of the failure].
286. The investigation of the cause of the nonconforming batch of a PET drug product did not include examination of the [processes] [operations] [records] [complaints] [other relevant sources of information] concerning the nonconforming product.
287. 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.
288. Vermin was observed in an area immediately adjacent to your production area.
289. Personnel did not [disinfect] [change gloves frequently enough] to prevent contamination.
290. Personnel engaged in aseptic processing were observed with [exposed hands] [exposed wrists] [exposed legs] [exposed hair] [exposed mouth].
291. Personnel [used a non-sterile tool on] [manually contacted the inner surface of] the container or closure.
292. Personnel were observed touching equipment or other surfaces located outside of the ISO 5 area with gloved hands and then proceeding with aseptic processing without changing or sanitizing gloves.
293. 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.
294. You did not make adequate product evaluation and take remedial action where actionable microbial contamination was found to be present in an area adjacent to the ISO 5 classified aseptic processing area during aseptic production.
295. Unsealed, loose ceiling tiles were observed in your cleanroom.
296. Your facility design allowed the influx of poor quality air into a higher classified area.
297. You had inadequate HEPA filter [coverage] [airflow] over the area to which sterile product was exposed.
298. Sinks or drains were present in the cleanroom where the ISO 5 classified aseptic processing area was located.
299. The [final] [intermediate] containers/closures used for drug product intended to be sterile have not been sterilized or depyrogenated.
300. The filter intended to render final product sterile [was not adequate to accomplish sterilization] [was not pharmaceutical grade].
301. The cycle parameters (temperature, pressure and time) used for heat sterilization of product intended to be sterile were not lethal to heat-resistant microorganisms.
302. [Equipment was] [Materials or supplies were] not disinfected prior to entering the aseptic processing areas.
303. An application holder did not [ensure healthcare providers (HCPs) who prescribe the drug are specially certified] [ensure mechanisms are in place that allow healthcare providers (HCPs) the ability to complete the certification process] [secure a database of certified healthcare providers (HCPs)] [identify and address non-compliant certified healthcare providers (HCPs)] [make training available to prescribing healthcare providers (HCPs)], as required by your approved REMS Element to Assure Safe Use (ETASU) A.
304. 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.
305. An application holder did not [ensure health care settings that dispense the drug are certified] [ensure mechanisms are in place that allow health care settings the ability to complete the certification process] [identify and address non-compliant certified health care settings], as required by your approved REMS Element to Assure Safe Use (ETASU) C.
306. An application holder did not ensure each patient receiving the drug has evidence or other documentation of safe-use conditions, as required by your approved REMS Element to Assure Safe Use (ETASU) D.
307. An application holder did not ensure each patient using the drug required by the REMS be enrolled in a registry, as required by your approved REMS Element to Assure Safe Use (ETASU) F.
308. 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.
309. 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.
310. [Beta-lactam drugs] [Hazardous drugs] [Highly potent drugs] were produced without providing adequate containment, segregation, and/or cleaning of work surfaces, utensils, and/or personnel to prevent cross-contamination.
311. Use of [ingredients] [processing aides] not intended for pharmaceutical use in sterile drug production.
Personnel infrequently [changed] [sanitized] gloves to prevent contamination.
312. [Sterile drugs] [Materials] were exposed to lower than ISO 5 quality air.
313. Personnel were observed moving quickly in a critical area or in an area immediately adjacent to a critical area likely causing disruption of unidirectional airflow.
314. Production areas have difficult to clean or contain porous, particle generating, or visibly dirty equipment or surfaces.
315. HEPA filters are not sealed around the perimeter.
316. Failure to appropriately and regularly clean and disinfect or sterilize equipment located in the ISO 5 area.
317. Lack of disinfection of [equipment] [supplies] at each transition from areas of lower quality air to areas of higher quality air.
318. Use of a disinfectant in a manner insufficient to achieve adequate levels of disinfection.
319. [Lack of] [Inadequate] routine environmental monitoring in the [ISO 5 area] [classified areas].
320. [Failure to conduct] [Inadequate] post-use filter-integrity testing on filters used to sterilize drug products.
321. The labels of your outsourcing facility's drug products do not include information required by section 503B(a)(10)(A) of the Federal Food, Drug, and Cosmetic Act (FD&C Act).
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