Data supporting the quality and safety of products must meet the ALCOA+ elements in order to avoid regulatory citations for data integrity issues, says Susan J. Schniepp, Distinguished Fellow, Regulatory Compliance Associates.
Q: I am familiar with the term ALCOA as it relates to data integrity, but lately, I have heard people refer to ALCOA+. Can you explain what impact this new acronym has on my company’s data integrity program?
A: Before we get into the reason for the additions to ALCOA, referred to as ALCOA+, we should review what both of the acronyms mean. The acronym ALCOA requires data be attributable, legible, contemporaneous, original, and accurate. The acronym ALCOA+ adds the concepts that, in addition to ALCOA, data also needs to be complete, consistent, enduring, and available. It is important to understand what each element of ALCOA and ALCOA+ mean in order to apply the concepts appropriately with respect to a company’s records. The following are some general definitions, paraphrased from the Pharmaceutical Inspection Co-operation Scheme (PIC/S), that can be used for understanding the elements of ALCOA and ALCOA+:
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- Attributable: The data generated or collected must be traceable back to the individual who generated the information.
- Legible: The data recorded must be readable and permanent.
- Contemporaneous: The results, measurements, etc. must be recorded at the time the work is performed.
- Original: Original or source data are the record, report, notebook etc. where the data point was initially recorded.
- Accurate: The data recorded must be complete, consistent, truthful, and representative of facts.
- Complete: Information that is critical to recreating and understanding an event. This would include any repeat or reanalysis performed on a laboratory test sample.
- Consistent: The data are presented, recorded, dated, or time-stamped in the expected and defined sequence.
- Enduring: The data or information must be maintained, intact, and accessible throughout their defined retention period.
- Available: The data or information must be able to be accessed at any time during the defined retention period.
Data integrity has always concerned regulatory authorities, but it is important to understand what is prompting the renewed discussion of ALCOA and the introduction of ALCOA+ when discussing data integrity issues. Many of the concepts for ALCOA have been captured in the regulations as far back as 1978. Since that time, the industry has changed dramatically. The generic-drug industry has grown and in the United States alone accounts for more than 80% of the prescriptions written today. Coupled with the emergence of biosimilars, virtual companies, contract manufacturing organizations, rapid advances in automation and information technology, and the globalization of the industry have resulted in reinterpretation of the attributes associated with maintaining the integrity of data throughout the product lifecycle, whether those data are generated from electronic, paper-based, or hybrid systems. In addition, there has been an increase in citations internationally by the FDA, European Medicines Agency (EMA), Medicines and Healthcare products Regulatory Agency (MHRA), World Health Organization (WHO), and other health authorities. These changes and increased violations have brought about a resurgence and need to reeducate the industry on the basic principles and concepts regarding the proper control of data used to support the quality and safety of medicines.
The ALCOA acronym has been used since the 1990s; however, the requirements governing data elements have been in regulations for a much longer period of time. EudraLex chapter 4 states, “Suitable controls should be implemented to ensure the accuracy, integrity, availability, and legibility of documents. Instruction documents should be free from errors and available in writing”. The US Code of Federal Regulations (CFR) refers to these elements in various sections of the regulations. An example for language speaking to the element of attributable is in 21 CFR 211.194(a), which states, “The initials or signature of the person who performs each test and the date(s) the tests were performed.” Language in 21 CFR 58.130 (e) addresses the elements of contemporaneous and legible by stating, “All data generated during the conduct of a nonclinical laboratory study, except those that are generated by automated data collection systems, shall be recorded directly, promptly, and legibly in ink. All data entries shall be dated on the date of entry and signed or initialed by the person entering the data.”
Recent documents issued by WHO and the PIC/S (1) have added to the original ALCOA attributes as indicated above. The PIC/S document actually states, “Some key concepts of GDocPs are summarized by the acronym ALCOA: Attributable, Legible, Contemporaneous, Original, and Accurate. The following attributes can be added to the list: Complete, Consistent, Enduring, and Available. Together, these expectations ensure that events are properly documented and the data can be used to support informed decisions.” WHO refers to ALCOA+ in the title of Appendix 1 to their 2018 document. The last two documents also address the concept of quality culture (10). The impact to your organization is that the quality culture must ensure that data supporting the quality and safety of your product must now meet the ALCOA+ elements in order to avoid regulatory citations for data integrity issues.
Vol. 43, No. 10