Data integrity has long played an important role in pharmaceutical production, with robust data collection and storage fundamental to the concept of Good Manufacturing Practice (GMP).
For many years, regulatory authorities such as the US Food and Drug Administration (FDA), European Medicines Agency (EMA), and China Food and Drug Administration (CFDA) have pointed to five key principles as a guide to their expectations around data integrity. These principles, known by the abbreviation ALCOA, guide good industry practice on matters from routine data collection through to documentation and training:
Attributable – Whether documenting data digitally or on paper, all data should be attributable to the individual who created it, and ideally, the instrument and time it was created too. Should a record be amended, it’s important to know by whom, when and why – with this latter point an important question that is often overlooked.
Legible – Data should withstand the test of time. It shouldn’t simply be readable over the duration of a research project or product lifecycle – it must still be legible in 20 or 30 years. This is also true of corrections – original data must be readable, even if it was erroneous, alongside why it was changed and what it was changed to.
Contemporaneous – Data should be documented at its point of creation – not at the end of the day, or even on returning to a write-up area. Prompt data collection, supported by automatic date and time stamps, ensures data is accurate and attributable.
Original – Regardless of whether data is subsequently transcribed into electronic format, original records or certified copies should be retained. For example, when collecting data using offline instruments such as mass balances, print-outs should still be archived or copied as evidence to protect the integrity of the original measurement.
Accurate – Finally, when it comes to data collection, what’s recorded must be what is observed. In other words, the record should be an honest account of the facts.
But as manufacturing workflows have become increasingly integrated and complex, regulatory bodies are demanding ever higher standards of data accuracy, security and completeness.
In the last couple of years, regulatory authorities including the FDA, EMA, and CFDA, have all announced new guidance designed to safeguard data quality throughout the pharmaceutical development process, including the testing, manufacturing and packaging of medicines, as well as their distribution and monitoring.
As a result of this increased scrutiny, some industry experts have suggested that data should be complete, consistent, enduring and available too. This expanded list of principles, known as ALCOACCEA or ALCOA+, highlights how quickly industry expectations can shift.
Towards an integrated, paperless system
Despite this increased regulatory focus, a surprisingly large number of manufacturers still rely on systems that are inefficient or disconnected from a data collection and management standpoint. Even in the most sophisticated pharmaceutical environments, many QA/QC labs still use physical notebooks that inherently expose data to human errors and misinterpretation. Some also employ paper-based systems to record data associated with raw materials, environmental measurements and even analytical methods. This fragmented approach to data management, often involving incompatible storage formats such as spreadsheets and proprietary software, can introduce errors, reduce operational efficiency and add an additional level of complexity to workflows.
For example, consider the potential for omissions and inconsistencies when lab personnel must adhere to standard operating procedures (SOPs) that are documented, maintained and distributed using paper-based systems. As well as being inherently inefficient, paper-based SOPs leave workflows vulnerable to human error by omitting steps in the process or by not performing them in the manner required. And when changes need to be made across a portfolio of SOPs to bring them into line with the latest methods, it can require significant time and resources to update each SOP.
Improving data integrity and compliance
As a result, many forward-looking companies are turning to integrated informatics solutions, comprising a laboratory information management system (LIMS), chromatography data system (CDS), laboratory execution system (LES) or procedural electronic laboratory notebook (ELN), and scientific data management system (SDMS) to manage this complexity and safeguard data integrity. Used together, these software solutions are helping research and manufacturing facilities not only meet current GMP, but prepare themselves for tomorrow’s rapidly changing data integrity requirements.
For example, by storing SOPs for chromatography workflows in electronic format in a LIMS, analysts have access to all relevant protocol parameters for an analytical workflow at the click of a button. Using a LIMS with an in-built LES or procedural ELN, operators can be taken step-wise through the SOP execution, the method parameters can be downloaded directly to the instrument and the chromatographic sequence initiated automatically by the CDS while the software records all actions and securely stores all collected data. Such integrated systems ensure analysts adhere to clearly defined protocols, obtain data of the highest levels of consistency and completeness, and provide an up-to-date record of who did what, when, and why.
Furthermore, using the advanced features built into highly integrated platforms, laboratories can even capture data such as reagent weights and pH meter readings alongside chromatographic data, method details, and audit trails, enabling all relevant information to be recalled at the click of a button.
Traceability from instrument to analyst
In addition to requirements around data quality and completeness, manufacturers are also under increased pressure to demonstrate traceability for process workflows, data which must be stored securely and available on demand if requested by auditors. Guidelines from the FDA, for example, recommend that audit trails capturing changes to critical data (such as those involving changes to sample run sequences and process parameters) are reviewed for every record and before each record’s final approval.
Integrated LIMS and CDS platforms offer functionality specifically for this purpose. Some options generate audit trails in real-time by capturing all actions made within the software. Modifications are permitted only by authorized personnel, and even then, the software retains prior data with the ability to display audit trails and object versions at the sequence, injection or file level, allowing users to quickly and conveniently review all changes, deletions and additions.
LIMS platforms with a built-in SDMS offer convenient paperless review and approval procedures and include advanced search and data mining tools to review chromatography and mass spectrometry data. These features can be used to review an instrument’s daily audit trails, search and filter for events, and add audits to reports for review. They can even determine when processes are drifting towards non-conformance, and give lab managers a complete overview of performance based on analyst, instrument or test.
A rapidly-changing outlook
As data becomes more complex and regulatory bodies expect ever higher standards of data integrity, pharmaceutical manufacturers are finding it’s simply not enough to meet the basic principles of data collection and management. Having an integrated informatics solution covering the entire lab workflow from sample reception to final results enables higher levels of data integrity than ever before but also allows for the automation, streamlining and control of many more operations and can deliver real-time knowledge of laboratory performance.
To avoid the penalties associated with regulatory non-compliance, many forward-looking life science companies are using the latest integrated informatics solutions to not only meet current guidelines, but prepare for tomorrow’s GMP too.
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