When developing a novel therapeutic drug, one of the most important tools at a researcher’s disposal is the data they create. Experimental data — gathered and analyzed using various instruments, including chromatography systems — facilitates the initial identification of target compounds, the refinement of potential new drugs and the demonstration of their efficacy for clinical trials.
The quality and integrity of this data is crucial for adhering to GMP regulations and, ultimately, delivering a safe and effective therapeutic drug to patients in a timely manner. This article explores how chromatography data systems (CDS) are helping the drug-making industry overcome many of the challenges faced when implementing technical controls to ensure the integrity of their data, creating greater confidence and allowing more time for product investigation.
The challenges of ensuring data integrity
According to the Food and Drug Administration (FDA), “data integrity refers to the completeness, consistency and accuracy of data.” This data should be attributable, legible, contemporaneously recorded, original or a true copy, and accurate, as well as complete, consistent, enduring and available throughout its life cycle — characteristics that make up the ALCOA+ principles.
Ensuring data integrity requires adhering not only to these principles, but also to sound scientific methods and good documentation practices. But maintaining the integrity of data throughout the drug development process comes with its own challenges.
During the development of a new drug, R&D laboratories accumulate massive amounts of experimental data from different sources. As the volume and complexity of data increases, so does the time and effort it takes to maintain the integrity of it all. While traditionally data integrity may not have been a primary focus for R&D laboratories, it is now seen as a crucial factor to be considered throughout the entire lifecycle of the drug product. Current regulatory thinking is that data integrity should be a foremost concern as soon as a company believes their product may become a drug used for treatment.
Moreover, data integrity regulations have become increasingly stringent over recent years, to ensure the safety, quality and efficacy of pharmaceutical products, and guarantee trust between the industry and consumers. With these strict regulations expected to continue and evolve, it is a time-consuming and demanding process to understand and effectively adapt to changing regulatory requirements from various agencies, including the FDA, the Medicines and Healthcare Products Regulatory Agency (MHRA) in the United Kingdom and the World Health Organization (WHO).
As part of regulatory guidelines, drug developers must incorporate the ALCOA+ principles into their workflows to ensure data integrity. This creates increasing overhead of ongoing documentation, validation and regular data review processes.
Another challenge involves legacy systems, which often have shared logins, insufficient level of detail for data reviews and basic audit trails with limited information — functions that do not take data integrity into account. Organizations may then need to resort to manual processes to comply with data integrity regulations, taking up valuable time.
Overcoming data integrity challenges with the help of advanced CDS software
Modern data management systems, such as CDS software, make it easier for drug developers to ensure data integrity. CDS software automatically keeps track of data, eliminating the need to manually trace it between different systems or documents. The software also puts digital restrictions in place for data capture and input, making it more difficult to manipulate or change data. With the right technical controls in place, electronic data is deemed more secure and reduces human error.
An advanced CDS software enables R&D scientists to better manage, store, track and review their data for improved integrity. With a system built with compliance in mind, drug developers can satisfy regulatory requirements without sacrificing efficiency. Modern CDS software offers the features below to help R&D laboratories ensure the integrity of their data.
Access controls: Modern CDS software allows system administrators to configure, implement and manage access controls, such as unique user accounts, privileges and access groups.
Unique user accounts mean no shared logins, making it easier to attribute actions to users and trace which individual performed a certain activity. In terms of security, administrators can monitor excessive failed login attempts for a specific user account or identify if a user is logged on in multiple locations at once — both of which may signal that an unauthorized user is trying to gain access to the system.
A CDS software normally employs a privileged-based approach to user management, where roles can be assigned to users to define what actions they can and cannot perform within the system. For instance, laboratory managers would typically be granted privileges to modify integration, while laboratory scientists might only have privileges to create and run sequences. Access groups may also be created to control access to specific data and instruments, with each group having its own set of privileges that define what members are allowed to see and use in the system. For example, the location of data generated by R&D scientists and QC analysts can be segregated from each other, or, the use of a specific mass spectrometer (MS) instrument may be limited to a specific group.
Audit trails: An audit trail is a vital regulatory requirement that records the “who, what, when and where,” of any activity and, with the appropriate settings, can even capture the “why.” Audit trails also act as the body of evidence to distinguish altered or invalid electronic records. Sophisticated CDS software has extensive audit trails covering data, instruments, user management and system administration to record historical changes and provide traceability, thereby making the audit trail review process simple and less onerous.
A forward-looking system like the Thermo Scientific Chromeleon CDS software, for instance, completely documents operations and modifications performed on data objects, including sequences, injections, processing methods, instrument methods, report templates and chromatograms. In addition to tracking changes, the software records versions of these objects and provides a quick way to view the differences between two versions, clearly flagging insertions, deletions and alterations, and any variation in the results. To maintain the integrity of the data, all previous versions remain read-only, with authorized users allowed to make modifications only for the most recent version.
Many critical GMP decisions, such as manufacturing mix times, product expiration dates, and acceptable impurity levels, need to be made using the data generated during drug development. With comprehensive audit trails, gaining a true understanding of your data, so that these decisions can be based on it, becomes even easier. What’s more, as the software captures in-depth information, scientists and reviewers will be able to swiftly and easily trace and identify all data that might have been affected if an issue arises, thereby focusing more of their time and effort on the science rather than problem-solving.
Data reviews: Modern CDS software provides scientists with a painless way to review data. Information, such as raw data, the associated methods and the order in which actions were performed, can be reviewed at a granular level. The full history of all data objects can also be reviewed, including every modification made, as well as the state of each variable related to a data object before and after a change was applied.
More granular data reviews allow for better traceability of information and an effortless means to take a look behind the final results to understand the process of by whom, when and why any changes were made. Additionally, this granularity enables the ALCOA+ principles to be easily integrated into laboratory workflows. Acquiring the raw data directly with the CDS ensures it is original and recording the full history of all objects and the order in which actions were performed ensures data is contemporaneous, accurate, complete, consistent, enduring and available.
Maintaining data integrity is crucial for complying with GMP regulations and ensuring the safety of therapeutic drugs for patients. But doing so can be challenging for R&D laboratories, who have to handle large volumes of data during drug development, adapt to evolving standards and incorporate ALCOA+ principles into their workflows — all especially difficult when using legacy systems that may not have been designed to adhere to data integrity guidelines.
Advanced CDS software helps drug developers overcome these challenges. Through configurable access controls, extensive audit trails and an effortless way to review data, CDS software not only makes it easier to comply with regulations, but also makes data integrity a smooth and seamless process. This allows drug developers to focus on the science and accelerate the development of potentially lifesaving drugs, confident in the integrity of their data.
Patrick Kenny is a product marketing specialist for chromatography software at Thermo Fisher Scientific. He holds a Bachelor’s Degree in Chemistry from the University of Massachusetts Dartmouth and Master’s Degree in Chemistry from the University of Massachusetts Amherst. Patrick spent 12 years in analytical chemistry lab management and director roles for a regulated pharma/medical device CMO before moving to a compounding pharmacy company to start their QC chemistry lab. In these roles, he represented the chemistry lab in FDA, EMA, ISO, QP and >100 client audits. Patrick’s extensive regulated-lab management experience gives him a unique insight into the challenges lab managers face on a daily basis. He uses this knowledge to help customers best utilize their software to achieve regulatory compliance while realizing high productivity.