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Pharmaceutical Technology QUALITY AND REGULATORY SOURCEBOOK EBOOK MARCH 2022 35 Development and manufacturing processes through- out drug production have become increasingly reliant on heavily automated equipment and computerized sys- tems. As a result, an abundance of data will be created for a single project. Ensuring DI—making sure data are complete, consis- tent, and accurate throughout its lifecycle—is essential to data quality and reliability. Using unreliable data in decision-making can negatively impact product qual- ity and patient safety and ultimately lead to disastrous consequences. These include safety risks, recalls, delays, denied drug approvals, remediation costs, and damage to the company's reputation. The need for regulations The potential risk to patients when unreliable data is used in decision-making spurred the introduction of DI-related regulations in the early 1960s by FDA, as mentioned previously. Additional regulations were introduced in the following years as techno- logical advancements progressed. In 1997, FDA published 21 CFR (Code of Federal Regulations) Part 11. This provides the regulatory requirements surrounding electronic records and signatures, including DI controls and computer- ized system validation. In 2011, the latest revision to EudraLex (the collection of rules and regulations governing medicinal products in the EU) Vol. 4, Annex 11 Computerised Systems was published as the European equivalent of 21 CFR Part 11. These are the major regulations currently governing elec- tronic records and DI controls that have helped shape various local regulations around the world. Numerous regulatory guidance from regulatory bodies, including the Medicines and Healthcare products Regulatory Agency, FDA, and the World Health Organization, have been produced over the years to reiterate and emphasize the message of the requirements outlined in Part 11 and Annex 11. In particular, FDA and other regulatory agencies have highlighted that complete, consistent, and accurate data need to be ALCOA—attributable, legible, con- temporaneous, original, and accurate. The ALCOA+ principles have an additional emphasis on ensuring data are complete, consistent, enduring, and available. The release of further guidance has predominantly been prompted in response to deficiencies identified during regulatory inspections, especially in the case of CDMOs. These deficiencies have included the absence of audit trails or inadequate control over laboratory computer systems (1). However, understanding and implementing the regulatory requirements of DI and the ALCOA+ principles in computerized systems re- main a challenge to many CDMOs today. Downfalls of a 'technology-first' approach Despite the availability of advanced technologies, the number of observations made regarding DI in docu- mentation and record management practices during inspections has increased in recent years (2). In the span of five years 2014–2018, 79% of FDA's global drug manufacturing warning letters cited DI, and the number of these warning letters citing DI increased more than times (2). Technologies used to record, manage, and store data that are well-implemented with robust DI controls can Technology is not the predominant challenge to achieving regulatory compliance, but the lack of critical thinking skills when designing a quality system.