A List of FDA 483 Observations in FY 2020
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. 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.
4. 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.
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. 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.
8. Procedures designed to prevent microbiological contamination of drug products purporting to be sterile are not [established] [written] [followed].
9. Established [specifications] [standards] [sampling plans] [test procedures] [laboratory control mechanisms] are not [followed] [documented at the time of performance].
10. Routine [calibration] [inspection] [checking] of [automatic] [mechanical] [electronic] equipment is not performed according to a written program designed to assure proper performance.
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. 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.
14. 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.
15. Aseptic processing areas are deficient regarding the system for monitoring environmental conditions.
16. 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].
17. There is no written testing program designed to assess the stability characteristics of drug products.
18. 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].
19. 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].
20. Laboratory records do not include complete data derived from all tests, examinations and assay necessary to assure compliance with established specifications and standards.
21. Employees engaged in the [manufacture] [processing] [packing] [holding] of a drug product lack the [education] [training] [experience] required to perform their assigned functions.
22. The [accuracy] [sensitivity] [specificity] [reproducibility] of test methods have not been [established] [documented].
23. There is no quality control unit.
24. The written stability testing program is not followed.
25. Aseptic processing areas are deficient regarding the system for cleaning and disinfecting the [room] [equipment] to produce aseptic conditions.
26. Procedures designed to prevent microbiological contamination of drug products purporting to be sterile did not include [adequate] validation of the [aseptic] [sterilization] process.
27. 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].
28. The quality control unit lacks authority to [review production records to assure that no errors have occurred] [fully investigate errors that have occurred].
29. Written production and process control procedures are not [followed in the execution of production and process control functions] [documented at the time of performance].
30. Buildings used in the [manufacturing] [processing] [packing] [holding] of a drug product are not maintained in a good state of repair.
31. Deviations from written production and process control procedures are not [recorded] [justified].
32. 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].
33. Procedures designed to prevent objectionable microorganisms in drug products not required to be sterile are not [established] [written] [followed].
34. Written records of major equipment [cleaning] [maintenance] [use] are not included in individual equipment logs.
35. Laboratory records are deficient in that they do not include a complete record of all data obtained during testing.
36. 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.
37. Written records are not [always] made of investigations into [unexplained discrepancies] [the failure of a batch or any of its components to meet specifications].
38. 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.
39. Each batch of drug product required to be free of objectionable microorganisms is not tested through appropriate laboratory testing.
40. 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.
41. Procedures describing the handling of all written and oral complaints regarding a drug product are not [established] [written] [followed].
42. Time limits are not established when appropriate for the completion of each production phase to assure the quality of the drug product.
43. 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].
44. Changes to written procedures are not [drafted, reviewed and approved by the appropriate organizational unit] [reviewed and approved by the quality control unit].
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. Master production and control records lack [complete manufacturing and control instructions] [sampling and testing procedures] [specifications] [special notations] [precautions to be followed].
47. GMP training is not conducted [on a continuing basis] [with sufficient frequency] to assure that employees remain familiar with CGMP requirements applicable to them.
48. Input to and output from [the computer] [related systems of formulas] [records or data] are not checked for accuracy.
49. Written procedures are lacking which describe in sufficient detail the [receipt] [identification] [storage] [handling] [sampling] [testing] [approval] [rejection] of [components] [drug product containers] [closures].
50. Drug products failing to meet established [standards] [specifications] [quality control criteria] are not rejected.
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. You used a non-pharmaceutical grade component in the formulation of a drug product.
53. The number of qualified personnel is inadequate to [perform] [supervise] the [manufacture] [processing] [packing] [holding] of each drug product.
54. Records are not kept for the [maintenance] [cleaning] [sanitizing] [inspection] of equipment.
55. 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].
56. Backup data is not assured as [exact] [complete] [secure from alteration, erasure or loss] through keeping hard copy or alternate systems.
57. You produced hazardous drugs without providing adequate [containment] [segregation] [cleaning of work surfaces] [cleaning of utensils] [cleaning of personnel] to prevent cross-contamination.
58. Failure to maintain a backup file of data entered into the computer or related system.
59. Separate or defined areas to prevent contamination or mix-ups are deficient regarding operations related to aseptic processing of drug products.
60. Aseptic processing areas are deficient regarding systems for maintaining any equipment used to control the aseptic conditions.
61. 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.
62. The written stability program for drug products does not include [reliable] [meaningful] [specific] test methods.
63. 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.
64. 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.
65. Procedures describing the handling of written and oral complaints related to drug products are [not written or followed] [deficiently written or followed].
66. 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.
67. Written procedures are not [drafted, reviewed and approved by the appropriate organizational units] [reviewed and approved by the quality control unit].
68. Procedures describing the calibration of instruments, apparatus, gauges and recording devices are [not written or followed] [deficiently written or followed].
69. 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.
70. Each component is not tested for conformity with all appropriate written specifications for purity, strength, and quality.
71. The suitability of all testing methods is not verified under actual conditions of use.
72. 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.
73. 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].
74. 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.
75. Records of the [calibration checks] [inspections] of automatic, mechanical or electronic equipment, including computers or related systems are not maintained.
76. Access to the storage area for labels and labeling materials is not limited to authorized personnel.
77. There was a failure to handle and store [components] [drug product containers] [closures] at all times in a manner to prevent contamination.
78. 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.
79. 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].
80. Drug product component testing is deficient in that at least one specific test to verify the identity of each component is not performed.
81. Procedures for the preparation of master production and control records are not [described in a written procedure] [followed].
82. The batch production and control records are deficient in that they do not include [complete labeling control records] [specimen] [copy] of labeling.
83. Complete records are not maintained of any modification of an established method employed in testing.
84. Laboratory records do not include complete records of any testing and standardization of laboratory [reference standards] [reagents] [standard solutions].
85. Complaint records are deficient in that they do not include the findings of the [investigation] [follow-up].
86. Washing and toilet facilities lack [hot and cold water] [soap or detergent] [air driers or single-service towels] [cleanliness].
87. Determinations of conformance to appropriate written specifications for acceptance are [not made] [deficient] for drug products.
88. 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.
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. 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].
91. Results of stability testing are not used in determining [appropriate storage conditions] [expiration dates].
92. 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].
93. 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.
94. Disinfecting agents and [cleaning pads] [cleaning wipes] used in the ISO 5 classified aseptic processing areas were not sterile.
95. The quality control unit lacks responsibility to [approve] [reject] all procedures or specifications impacting on the [identity] [strength] [quality] [purity] of drug products.
96. 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.
97. Procedures for the cleaning and maintenance of equipment are deficient regarding the protection of clean equipment from contamination prior to use.
98. 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.
99. The distribution system is deficient in that each lot of drug product cannot be readily determined to facilitate its recall if necessary.
100. 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.
101. Test procedures relative to appropriate laboratory testing for [sterility] [pyrogens] are not [written] [followed].
102. 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.
103. Deviations from written [specifications] [standards] [sampling plans] [test procedures] [laboratory mechanisms] are not [recorded] [justified].
104. Drug product samples are not [representative of the entire batch] [properly identified].
105. Written procedures for sanitation are not followed.
106. Each lot of [components] [drug product containers] [closures] was not appropriately identified as to its status in terms of being quarantined, approved or rejected.
107. Procedures describing the warehousing of drug products are not [established] [followed].
108. Written procedures for sampling and testing plans are not followed for each drug product.
109. You did not retain reserve samples for drug products for one year after the expiration dates of the drug products.
110. 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].
111. 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.
112. 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.
113. You did not [establish] [follow] written quality assurance procedures.
114. Personnel donned gowning apparel improperly, in a way that may have caused the gowning apparel to become contaminated.
115. The ISO 5 classified aseptic processing areas had [difficult to clean] [particle-generating] [visibly dirty] equipment or surface.
116. Your facility was designed and/or operated in a way that permits poor flow of [personnel] [materials].
117. Your facility design allowed the influx of poor quality air into a higher classified area.
118. 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.
119. The quality control unit lacks responsibility for approving or rejecting drug products [manufactured] [processed] [packed] [held] under contract by another company.
120. 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.
121. 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.
122. The [separate or defined areas] [control systems] necessary to prevent contamination or mix-ups are deficient.
123. Procedures for the cleaning and maintenance of equipment are deficient regarding maintenance and cleaning schedules, including, where appropriate, sanitizing schedules.
124. Procedures for the cleaning and maintenance of equipment are deficient regarding inspection of the equipment for cleanliness immediately before use.
125. 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.
126. 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.
127. Each component is not added to a batch by one person and verified by a second person.
128. 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.
129. 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.
130. Separate or defined areas to prevent contamination or mix-ups are deficient regarding the manufacturing and processing operations.
131. Aseptic processing areas are deficient in that [floors] [walls] [ceilings] are not smooth and/or hard surfaces that are easily cleanable.
132. Aseptic processing areas are deficient regarding air supply that is filtered through high-efficiency particulate air filters under positive pressure.
133. Strict control is not exercised over labeling issued for use in drug product labeling operations.
134. Procedures describing in sufficient detail the controls employed for the issuance of labeling are not [written] [followed].
135. Inspection of the [packaging] [labeling] facilities immediately before use is not done to assure that all drug products have been removed from previous operations.
136. Samples of representative units were not [collected] [visually examined] for correct labeling at the completion of finishing operations.
137. Incoming [components] [drug product containers] [closures] are not stored under quarantine until they have been tested or examined, as appropriate, and released.
138. Representative samples are not taken of each shipment of each lot of [components] [drug product containers] [closures] for testing or examination.
139. 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.
140. Component testing is deficient in that each component is not tested for conformity with all appropriate written specifications for purity, strength, and quality.
141. Each lot of a [component] [drug product containers] [closures] liable to objectionable microbiological contamination is deficiently subjected to microbiological tests before use.
142. 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].
143. Each batch of drug product purporting to be [sterile] [pyrogen-free] is not laboratory tested to determine conformance to such requirements.
144. 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.
145. 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].
146. The batch production and control records are deficient in that they do not include [in-process] [laboratory] control results.
147. The batch production and control records are deficient in that they do not include a statement of the [actual yield] [percentage of theoretical yield].
148. 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].
149. 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].
150. Complaint records are deficient in that they do not document the reason and the individual making the decision not to conduct a complaint investigation.
151. Specific identification tests are not conducted on components that have been accepted based on the supplier's report of analysis.
152. Components for drug product manufacturing are not [weighed] [measured] [subdivided as appropriate].
153. Each component is not added to the batch by one person and verified by a second person.
154. 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].
155. Written procedures are not followed for the [receipt] [identification] [storage] [handling] [sampling] [testing] [approval] [rejection] of [components] [drug product containers] [closures].
156. 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].
157. Batch production and control records do not include complete labeling control records, including specimens or copies of all labeling used for each batch of drug product produced.
158. 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.
159. 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.
160. Written records of investigation of a drug complaint do not include [the findings of the investigation] [the follow-up].
161. Written procedures have not been developed for the [surveillance] [receipt] [evaluation] [reporting to FDA] of post marketing adverse drug experiences.
162. 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].
163. 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.
164. 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.
165. Your laboratory analytical methods are not [suitable for their intended use] [sufficiently sensitive] [sufficiently specific] [sufficiently accurate] [sufficiently reproducible].
166. You implemented a new test procedure in a specification, but you did not first [establish] [document] the [accuracy] [sensitivity] [specificity] [reproducibility] of the procedure.
167. You did not take [appropriate] action to correct any identified problems to prevent recurrence of a nonconforming product or other quality problem.
168. The labels of your outsourcing facility's drug products are deficient.
169. Non-microbial contamination was observed in your production area.
170. Personnel [used a non-sterile tool on] [manually contacted the inner surface of] the container or closure.
171. Unsealed, loose ceiling tiles were observed in your cleanroom.
172. The [ISO 5 classified aseptic processing areas] [segregated production areas surrounding the ISO 5 classified aseptic processing area] contained dust-collecting overhangs without adequate and frequent cleaning.
173. HEPA filters were not sealed around each perimeter to the support frame.
174. [Equipment was] [Materials or supplies were] not disinfected prior to entering the aseptic processing areas.
175. The preparation of your master production and control records was not [described in a written procedure] [followed in accordance with your written procedure].
176. You did not [establish] [maintain] [follow] written procedures describing the [receipt] [login] [identification] [storage] [handling] [testing] [acceptance and/or rejection] of [components] [drug product containers] [closures].
177. Unauthorized personnel have access to enter areas of the buildings and facilities designated as limited access areas.
178. Employees with [apparent illness] [open lesions] are not excluded from direct contact with [components] [drug product containers] [closures] [in-process materials] [drug products] until the condition is [corrected] [determined by competent medical personnel not to jeopardize the safety or quality of drug products].
179. Procedures for the cleaning and maintenance of equipment are deficient regarding the removal or obliteration of the previous batch identification.
180. Component [weighing] [measuring] [subdividing] operations are not adequately supervised.
181. 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.
182. Separate or defined areas to prevent contamination or mix-ups are deficient regarding operations related to the storage of drug products after release.
183. Separate or defined areas to prevent contamination or mix-ups are deficient regarding laboratory controls and operations.
184. Deviations from production time limits [are not justified] [are not documented] [compromise the quality of the drug product].
185. 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].
186. There is a lack of written procedures describing in sufficient detail the [receipt] [identification] [storage] [handling] [sampling] [examination] [testing] of labeling and packaging materials.
187. Labeling and packaging materials are not [representatively sampled] [examined] [tested] upon receipt and before use in packaging and labeling of a drug product.
188. Discrepancies found outside preset limits when reconciling the quantities of labeling issued, used and returned, were not [evaluated] [investigated].
189. Procedures designed to assure that correct [labels] [labeling] [packaging materials] are used for drug products are not [written] [followed].
190. There is insufficient physical or spatial separation from operations and other drug products to prevent mix-ups and cross-contamination.
191. Examination of packaging and labeling materials for suitability and correctness before packaging operations is [not performed] [not documented in the batch production records].
192. 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.
193. 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].
194. The [number of containers to be sampled] [amount of material taken from each container] is not based upon appropriate criteria.
195. Sampling procedures are deficient regarding sampling components from the top, middle, and bottom of container.
196. 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.
197. 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.
198. Sampling and testing plans for drug products are not described in written procedures which include the [method of sampling] [number of units per batch to be tested].
199. 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.
200. The written stability program for drug products does not describe the storage conditions for samples retained for testing.
201. 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.
202. Accelerated stability studies, combined with basic stability information, used to support tentative expiration dates are not supported with ongoing full shelf life studies.
203. Procedures are not established which are designed to assure that the responsible officials of the firm, if they are not personally involved in or immediately aware of such actions, are notified in writing of [investigations conducted] [recalls] [reports of inspectional observations issued by FDA] [any regulatory actions brought by FDA relating to good manufacturing practices].
204. Individual equipment logs do not show [time] [date] [product] [lot number of each batch processed].
205. The entries in the equipment cleaning and use logs are not in chronological order.
206. 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].
207. 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].
208. 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].
209. The master production and control records are deficient in that they lack a justification for the variation in the amount of components used in the preparation of a dosage form.
210. Laboratory records are deficient in that they do not include a statement of the [weight] [measure] of the sample used for testing.
211. Laboratory records are deficient in that they do not include all calculations performed during testing.
212. Laboratory records are deficient in that they do not include the [initials] [signature] of the person performing the tests and the dates the tests were performed.
213. Laboratory records are deficient in that they do not include the [initials] [signature] of the second person reviewing the record for accuracy.
214. Adequate exhaust systems or other systems to control contaminants are lacking in areas where air contamination occurs during production.
215. The plumbing system contains defects that could contribute to the contamination of drug products.
216. Washing and toilet facilities are not [provided] [easily accessible to working areas].
217. 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.
218. 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].
219. 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.
220. The in process control procedures were deficient in that they did not include an examination of the adequacy of mixing to assure uniformity and homogeneity.
221. In-process specifications are not [consistent with drug product final specifications] [derived from previous acceptable process average and process variability estimates where possible] [determined by the application of suitable statistical procedures where appropriate].
222. Rejected in-process materials are not [identified] [controlled under a quarantine system] to prevent their use in manufacturing or processing operations for which they are unsuitable.
223. 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.
224. Determinations of conformance to appropriate written specifications for acceptance are [not made] [deficient] for in-process materials.
225. Test devices are deficient in that [instruments] [apparatus] [gauges] [recording devices] not meeting established specifications are used.
226. Reserve samples of OTC drug ingredients are deficient in that they are not retained for at least three years after the distribution of the last batch which contained the ingredient of OTC drugs exempt from expiration dating.
227. OTC drug product reserve samples exempt from bearing an expiration date are not retained for three years after the lot or batch of drug product is distributed.
228. 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.
229. Certificates of testing of [containers] [closures] are accepted in lieu of testing without [a visual identification] [establishing the reliability of the supplier's test results through appropriate validation of the test results at appropriate intervals].
230. Reprocessing procedures lack the steps to be taken to insure that reprocessed batches will conform with all established standards, specifications, and characteristics.
231. Results of inspection of packaging and labeling facilities are not documented in the batch production records.
232. Written distribution procedures are not [established] [followed].
233. 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.
234. 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.
235. Written specifications for laboratory controls do not include a description of the [sampling] [testing] procedures used.
236. Samples taken of in-process materials for determination of conformance to specifications are not [representative] [properly identified].
237. Samples taken of drug products for determination of conformance to written specifications are not [representative] [properly identified].
238. The use of [instruments] [apparatus] [gauges] [recording devices] not meeting established specifications was observed.
239. The statistical quality control criteria fail to include appropriate [acceptance levels] [rejection levels].
240. Where data from accelerated studies was used to project a tentative expiration date beyond a date supported by actual shelf life studies, there were no [stability studies] [drug product testing at appropriate intervals] conducted until the tentative expiration date was verified or the appropriate expiration date determined.
241. 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.
242. Non-penicillin drug products were not tested for the presence of penicillin, when a reasonable possibility existed that a non-penicillin drug product has been exposed to a cross-contamination with penicillin.
243. Batch production and control records for each batch of drug product produced do not include an accurate reproduction of the appropriate master production or control record which was checked for accuracy, dated and signed.
244. Batch production and control records do not include the identification of the persons [performing] [directly supervising] [checking] each significant step in the operation, for each batch of drug product produced.
245. 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.
246. The written record did not include the [reason an investigation was found not to be necessary] [name of the responsible person making the determination not to conduct an investigation] when an investigation into [unexplained discrepancies] [the failure of a batch or any of its components to meet specifications] was not conducted.
247. Written procedures describing the handling of all written and oral complaints do not include provisions for review to determine whether the complaint represents a serious and unexpected adverse drug experience which is required to be reported to the Food and Drug Administration.
248. 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].
249. Master production and control records lack [a description of the drug product containers, closures and packaging materials] [a specimen or copy of each label and all other labeling] [the signatures and dates entered by the person or persons responsible for the approval of labeling].
250. Records maintained of any modification of an established method employed in testing do not include [the reason for the modification] [the data to verify that the modification produced results that are at least as accurate and reliable for the material being tested as the established method].
251. Laboratory records of methods of testing used do not [indicate the method] [provide the reference] when employing methods in [recognized standard references] [an approved new drug application and the referenced method is not modified].
252. Laboratory records do not include a record of all calculations performed in connection with the test.
253. Adverse drug experience information has not been reported to FDA.
254. 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.
255. Not all annual periodic adverse drug experience reports have been submitted within 60 days of the anniversary date of the approval of the application.
256. A postmarketing 15-day Alert report based upon scientific literature was not accompanied by a copy of the published article.
257. 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.
258. Written procedures have not been developed for the [surveillance] [receipt] [evaluation] [reporting to FDA] of postmarketing adverse drug experiences.
259. You lack [a sufficient number of] personnel with the necessary [education] [background] [training] [experience] to perform their assigned functions.
260. You did not demonstrate that any change does not adversely affect the [identity] [strength] [quality] [purity] of your PET drug.
261. You did not establish appropriate written specifications for the [identity] [quality] [purity] of components.
262. You used [a lot] [lots] of [components] [containers] [closures] in PET drug production [which did not meet specifications] [which did not meet the expiration date] [which had not yet received material release].
263. You did not have master production and control records that document all steps in the PET drug production process.
264. 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.
265. You did not document the [calibration] [inspection] [checking] [maintenance] of laboratory equipment.
266. Each laboratory used to perform tests related to the production of a PET drug did not keep complete records of all tests performed to ensure compliance with established specifications and standards, including examinations and assays.
267. You did not [establish] [follow] [maintain] a written testing program to assess the stability characteristics of your PET drug products.
268. You used an established compendial test procedure in a specification, but you did not first [verify] [document] that the test works under the conditions of actual use.
269. All records and documentation required to be kept for PET drug products are not maintained for a period of at least 1 year from the date of final release, including conditional final release.
270. The container labels of your outsourcing facility's drug products are deficient.
271. Vermin was observed in your production area.
272. Your firm produced drugs while construction was underway in an adjacent area without adequate controls to prevent contamination of the production environment and product.
273. Personnel engaged in aseptic processing were observed wearing non-sterile gloves.
274. Personnel engaged in aseptic processing were observed with [exposed hands] [exposed wrists] [exposed legs] [exposed hair] [exposed mouth].
275. Personnel performed aseptic processing outside of an ISO 5 classified aseptic processing area.
276. 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.
277. 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.
278. You did not have a HEPA filter over the area to which sterile product was exposed.
279. You had inadequate HEPA filter [coverage] [airflow] over the area to which sterile product was exposed.
280. Sinks or drains were present in the cleanroom where the ISO 5 classified aseptic processing area was located.
281. The filter intended to render final product sterile [was not adequate to accomplish sterilization] [was not pharmaceutical grade].
282. Sporicidal agents were not used in your facility's cleanrooms and/or ISO 5 classified aseptic processing area.
283. The use of sporicidal agents in the [cleanrooms] [ISO 5 classified aseptic processing] area was [inadequate] [infrequent].
284. Disinfectant contact time (also known as "dwell time") and coverage of the item being disinfected were insufficient to achieve adequate levels of disinfection.
285. Your examination and testing of samples did not assure that the drug product and in-process material conformed to specifications.
286. You did not [distribute the Communication Plan in accordance with the distribution dates in the REMS] [distribute the Communication Plan to the targeted audience described in the REMS] [use the Communication Plan distribution methods described in the REMS], as required by your approved REMS Communication Plan.