Issue link: http://www.e-digitaleditions.com/i/1222740
12 Pharmaceutical Technology REGULATORY SOURCEBOOK MARCH 2020 P h a r mTe c h . c o m Data Integrity • Available: The data or information must be able to be accessed at any time during the de- fined 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 discuss- ing data integrity issues. Many of the concepts for ALCOA have been captured in the regulations as far back as 1978. A growing industry Since that time, the industry has changed dra- matically. The generic-drug industry has grown and, in the United States alone, accounts for more than 80% of the prescriptions written today (2). Coupled with the emergence of biosimilars, vir- tual companies, contract manufacturing organi- zations, rapid advances in automation and infor- mation technology, and the globalization of the industry have resulted in reinterpretation of the attributes associated with maintaining the in- tegrity of data throughout the product lifecycle, whether those data are generated from electronic, paper-based, or hybrid systems. In addition, t here has been a n increase in citat ions i nter nat iona l ly by t he FDA, Eu ro- pea n Med ici nes Agenc y (EM A), Med ici nes and Hea lt hcare products Regu lator y Agency (MHR A), World Health Organization (WHO), and ot her hea lt h aut horities. 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. Data integrity regulations 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" (3). 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. The US Code of Federal Regulations (CFR) refers to these elements in various sections of the regula- tions (4–8). An example for language speaking to the element of attributable is in 21 CFR 211.194(a) (7), 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 collec- tion 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."