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Pharmaceutical Technology Regulatory Sourcebook October 2020 37 to ensure the integrity of the data generated and retained. ALCOA requirements are discussed in FDA, Medicines and Healthcare products Regula- tory Agency, and Pharmaceutical Inspection Co- operation Scheme data integrity guidance docu- ments (2, 4, 5), and a partial attempt at discussing ALCOA+ is presented in the World Health Orga- nization guidance (3). This WHO Guide has the best explanation of the ALCOA principles, but the + criteria are inferred. The ALCOA+ criteria are defined as follows. The complete data analytical record should com- ply with the nine ALCOA+ data integrity require- ments applicable over the data lifecycle outlined in a European Medicines Agency (EMA) ref lec- tion paper on electronic source data (21) and are defined as: • Attributable: Identification of the individual who performed an activity. • Legible: Can you read and understand the elec- tronic data together with any associated metadata or all written entries on paper? Legible should also extend to any original data that has been changed or modified by an authorized individual so that the original entry is not obscured. • Contemporaneous: Documented (on paper or electronically) at the time of an activity. • Original: A written observation or printout or a certified copy thereof or an electronic record including all metadata of an activity. • A c c u r a t e : N o e r r o r s i n t h e o r i g i n a l observation(s) and no editing without docu- mented amendments/audit trail entries by au- thorized personnel. Accuracy is ensured and verified by documented review including re- view of audit trails. • Complete: All data from an analysis includ- ing any data generated including original data, data before and after repeat testing, reanalysis, modification, re-calculation, re-integration, and deletion. For hybrid systems, the paper out- put must be linked to the underlying electronic records used to produce it. • Consistent: All elements of the primary analyti- cal record, such as the sequence of events, are in sequence and do not contradict each other (i.e., documented chronologically). Data files are date- (all processes) and time- (when using paper, a hybrid, or electronic systems) stamped in the expected order. • Enduring: Recorded on authorized media (e.g., laboratory notebooks, numbered worksheets for which there is accountability, or electronic media that can last throughout the record re- tention period). • Available: The complete collection of records can be accessed or retrieved for review and audit or inspection over the lifetime of the record. These first five criteria were developed initially by Stan Wollen, an FDA inspector (ALCOA) (22) and the additional criteria by the EMA when dis- cussing integrity criteria for electronic source data from clinical studies (ALCOA+) (21). Interpreting pharmacopeial requirements for USP <731> How can a USP general chapter be best interpreted? Figure 4 shows the authors' proposal; on the left-hand side are three inputs: trained and competent ana- lysts, a data integrity policy, and USP General Chap- ter <1029> on Good Documentation Practices. The USP betamethasone valerate monograph requirement for LOD requires inputs from the general notices as well as the following general